Pandemic (H1N1) 2009 Master Update Sept 6 2009

Pandemic (H1N1) 2009 Virus (Quadruple Reassortment) “The 2009 Pandemic!” By Michael Fraser RN Of Irish First Point Responder Institute “Republic of Ireland” Medical Management of Biological Casualties 9/6/2009 Revised and Modified 18/07/2009

Mission of Presentation “To provide the people of Ireland a universal teaching aid to respond to Pandemic (H1N1) 2009 Virus” 9/6/2009 Please comment on Slide show for improvements ! 2

Virus Names Associated Pandemic Influenza 2009 • Swine-Origin Influenza Virus (S-OIV) (US) • North-American Influenza (Mexico) (WHO,OIE) • Mexican Virus (Israel +South Korea) • Mexican Flu (Netherlands) • Swine Influenza A(H1N1) • H1N1 flu/new flu (Taiwan) • Novel Influenza A(H1N1) (US/CDC) • Nouvelle Grippe A (H1N1) Spanish • A(H1N1)-SOIV (swine origin influenza virus) • Influenza A(H1N1)swl (Swine like) (US/CDC) • Influenza A(H1N1)swol (Swine origin like) • Influenza A (H1N1)v (Varient) May 3 2009 (ECDC) • Influenza A(H1N1) May 8 2009 (WHO) • Influenza A(Pandemic H1N1) virus (WHO/NRVESS) • Influenza A(H1N1)qr (Quadruple Reassortment) (IFPRI) • July, 7, 2009, Update: • Official name by (WHO, FAO and OIE): “Pandemic (H1N1) 2009” Virus will be referred to at different points of Presentation! 9/6/2009 3

Pandemic (H1N1) 2009 Objectives • Identify Who pandemic Phases In relation to too European and Irish Alert Levels • Identify Global Health Regulation for Ireland • Biological triage • Identify global and Irish Influenza Surveillance Systems • Overview of new mitigation strategies from WHO,DOHC briefing! • Pandemic Influenza A(H1N1) 09 Virus Worldwide Epidemiology • Surveillance processes and systems • Zoonosis of Swine Pandemic Influenza A(H1N1) 09 Virus Signs and Symptom Post-mortem findings, Past Outbreaks and differences of Swine Influenza Virus (SIV) and Pandemic Influenza A(H1N1) 09 Virus /Seasonal Influenza Virus • Influenza virus antigenic shift and drift • Categorizing Influenza Virus “Viral Nomenclature • Emergence of Some Influenza Viruses in Humans • Swine Influenza (SIV) Reassortment • Swine Influenza Host Range • Pathogenesis of Triple Reassortment and Quadruple Reassortment 9/6/2009 4

Pandemic (H1N1) 2009 Objectives • Containment and mitigation definition and strategies • Public health “containment" and “mitigation” management • Reporting Pandemic Influenza A(H1N1) 09 Virus in “containment” and “mitigation” phases • Infection Control and Prevention for Health Care Facilities • Epidemiological Risk Factors Influenza A(H1N1) • Specific Investigational Triggers confirmed Pandemic Influenza A(H1N1) 09 Virus • Irish resources for Pandemic Influenza A(H1N1) 09 Virus • Pandemic Influenza A(H1N1) 09 Virus Transmission, Personal Prevention, Human Signs and Symptoms, High Risk Groups, Diagnosis, Case Definitions 9/6/2009 5

Pandemic (H1N1) 2009 Objectives Continued • Recommended Initial PPE Protection Levels for all levels of response • Handling Human Remains (HHR) • Pandemic Influenza A(H1N1) 09 Virus Antivirals Treatment Schedule,Adverse Effects – Special Considerations for Children – Pregnancy – Typical Antiviral Clinic Process Flow Chart • Post Exposure Prophylaxis (PEP) • Pandemic Influenza A(H1N1) 09 Virus Irelands Laboratories Overview, Specimen Collection, Laboratory Precautions, • Shipping Infectious Substances (WHO “E-tool” guidelines) • Infection Control In Health Care Setting • Point of Care Risk Assessment Tool for Pandemic (H1N1) 2009 Flu Virus • Environmental Waste 9/6/2009 6

Pandemic (H1N1) 2009 Objectives Continued • Vaccine development process and timeline • Antiviral treatments and considerations ,(PIEG) On Antivirals Algorithms during “containment” and “mitigation” phases • Bioethics • Infection Prevention and Control Guidance for the Ambulance Service • School outbreaks and containment and mitigation strategies – Public Health hyperlinks – Department of Education hyperlinks – Educational tools with hyperlinks – Pandemic Checklist for Irish School JI-6 th Year • Residential day camps recommendations for the surveillance of Influenza-like illness • Pandemic (H1N1) 2009 Virus Business Continuity with checklist • Case Studies: • England's (DH) - Planning assumptions in context to Pandemic (H1N1) 2009 (Sept 3 2009) • Mexico “Estimated Ratio” • Closing Discussion 9/6/2009 7

World Health Organization (WHO) Pandemic Phase Advisories 11th June 2009 Influenza pandemic alert level raised to Phase 6 The Director-General of WHO Dr Margaret Chan has therefore decided to raise the level of influenza pandemic alert from phase 5 to phase 6. "The world is now at the start of the 2009 On April 27 2009 The World Health Organisation influenza pandemic," On April 29, the Emergency Committee raised its pandemic alert level to 4, verifying human- had their third meeting, and decided to to-human swine flu, hours after the first British cases raise the pandemic alert level to five, the of the disease were confirmed. April 28 2009 second-highest level, indicating that a WHO flu expert Keiji Fukuda pointed out that it is too pandemic is "imminent," and that late to contain the swine flu "Containment is not a feasible operation. Countries human-to-human transmission cases should now focus on mitigating the effect of the have been recorded in multiple virus,” countries. Pandemic Influenza Phases 3 to 4 Phase PHASES 5-6/ 4 to 5 Phase April 27 2009 PANDEMIC April 29 2009 PHASES 4 POST PEAK POST PHASES 1-3 PANDEMIC Time Predominately Sustained Widespread Possibility Disease Animal Human to Human of recurrent Activity at Infections Human Infection Events Seasonal Few Human Transmission Levels Infections 9/6/2009 Avian Influenza H5N1 Phase 1-3 8

World Health Organization (WHO) Pandemic Phase Advisories Phase 6 Rationale • World Health Organization has raise the H1N1 flu virus pandemic alert level from Phase Five to Phase Six. In doing so the WHO underscored: • The decision is based on the spread of the virus and not the severity of illness it causes. The virus has caused sustained community level outbreaks in more than three countries across two WHO regions • In general, the “Pandemic (H1N1) 2009” flu virus continues to cause moderate illness globally with most people affected recovering at home without medical treatment. • 88-98 % are mild cases and 1-2% are severe cases related to underlying co- morbid conditions complicating the treatment regime • For instance in Ireland most infections to date have been mild! • Future severity assessments will reflect one or a combination of the following factors: – changes in the virus – underlying vulnerabilities – limitations in health system capacities WHO Headquarters in Geneva 9/6/2009T 9

Pandemic (H1N1) 2009 in Context to the Declaration of Pandemic Phases The 2009 pandemic was declared due to geographical spread (rather than severity) over the WHO defined regions Generic Global On Saturday, 25 April, upon the advice of the Emergency Committee called under the rules of the International Health Pandemic Curves Regulations, the Director-General declared this event a Public Health Emergency of International Concern.(PHEIC) AMRO- Country A: Mexico Pandemic Pandemic Phase 4 AMRO: Country B: United States/ C: Canada Declared April 27 2009 Euro: Country D: Spain/ E: England WPRO : Country F: New Zealand Pandemic Phase 5 Declared April 29 2009 EMRO: Country G: Israel (Pandemic Imminent) WHO Regions AMRO Euro 4 WHO regions with Pandemic Phase 6 WPRO multiple countries with Declared June 11 sustained community EMRO transmissions 2009 SEARO AFRO Phase 4 Phase 5 Phase 6 April 27 2009 April 29 June 11 2009 2009 Phase 4 2009 Human to human transmission of an animal influenza reassortant virus able to sustain- community level outbreaks has been verified Phase 5 2009 The virus has caused sustained community outbreaks in two or more countries in one WHO region Phase 6 2009 The virus has caused sustained community level outbreaks in at least another country in an another WHO region in addition to the criteria defined in Phase 5 9/6/2009 The move to pandemic phase 6 is a response to the fact that according to WHO the spread of influenza A(H1N1)v in several countries can no longer be 10 traced to clearly-defined chains of human-to-human transmission and that the scientific criteria for an influenza pandemic have been met.

International Health Regulations • Following 2003 SARS, the World Health Organization (WHO) revised the International Health Regulations • IHR contains an operational definition of a “public health emergency of international concern” that triggers increased control responsibilities for nations and specifically components of surveillance • 194 countries worldwide • As of 4th,August, 2009 – 177 countries have confirmed cases of Pandemic (H1N1) 2009 9/6/2009 11

National Surveillance Components for Ireland National Surveillance Components for Ireland Early detection and Investigation according to International Health Comprehensive Planning Regulations Pandemic monitoring Cases Epidemic Curve at National Level New influenza virus sub‐types and clusters of unknown and unusual disease are notifiable to WHO in accordance with the Annex 2 decision instrument of the IHR (2005) Time Graph adapted from IHR 2005 9/6/2009 12

WHO Pandemic Phase Descriptions and Main Actions by Phase 2009 Estimated Probability of Description Main Actions in Main Actions in Not-Yet-Affected Pandemic Affected Countries Countries Phase 1 No animal influenza virus circulating among animals has been reported to cause infection in humans. Phase 2 An animal influenza virus Producing, implementing, exercising, circulating in domesticated or wild animals is known to and harmonizing national pandemic Uncertain have caused infection in humans and is therefore influenza preparedness and response considered a specific plans with national emergency potential pandemic threat. preparedness and response plans. Phase 3 An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Phase 4 Human-to-human transmission of Medium an animal or human-animal Rapid Readiness for to high influenza reassortant virus able to containment. pandemic sustain community-level outbreaks response. has been verified. Phase 5 The same identified virus has caused High to sustained community level certain outbreaks in at least two countries Pandemic in one WHO region. response: Each country to Readiness for Phase 6 In addition to the criteria defined in implement actions imminent Pandemic in Phase 5, the same virus has caused as called for in their response. progress sustained community level outbreaks national plans. in at least one other country in another WHO region. Post-Peak Period Levels of pandemic influenza in Evaluation of most countries with adequate response; recovery; surveillance have dropped below preparation for peak levels. possible second wave. Possible New Wave Level of pandemic influenza activity in most countries with adequate Response surveillance is rising again Post-Pandemic Period Levels of influenza have returned Evaluation of to the levels seen for seasonal response; influenza in most countries with revision of plans; adequate surveillance. recovery. 9/6/2009 13

Who Pandemic Phases and Irelands Recommended Actions Preparedness Phase 1-3 Phase 4 Phase 5-6 Phase-Post Peak Phase-Post Pandemic Components Planning and Coordination Develop, exercise, and Direct and coordinate rapid Provide leadership and Plan and coordinate Review lessons learned and Share Periodically revise Pandemic containment coordination to for additional experiences with the international national Influenza activities in collaboration Multisectoral resources resources and community. pandemic preparedness with WHO to limit or delay to mitigate the societal capacities during Replenish resources. and response plans. the spread of infection. and economic impacts. possible future waves. Situation Monitoring and Develop robust national Increase surveillance. Actively monitor and Continue surveillance Evaluate the Pandemic Assessment Surveillance systems in Monitor assess the evolving to Detect Subsequent Characteristics and situation collaboration with Containment operations. pandemic and its waves. monitoring and assessment tools for national animal health Share findings with WHO impacts and Mitigation the next pandemic and other public authorities, and and the international measures. Health emergencies. other relevant sectors. community. Communications Complete Promote and communicate Continue providing Regularly update the Publicly acknowledge contributions communications Recommended updates to general public and other of all communities and sectors and planning and initiate interventions to public and all stakeholders on any communicate the lessons learned; communications prevent and reduce stakeholders on the changes to the status Incorporate lessons learned into activities to population and individual state of pandemic and of the pandemic. Communications activities and communicate real and risk. measures to mitigate planning for the next major public potential risks. risk. health crisis. Reducing the Spread of Promote beneficial Implement rapid pandemic Implement individual, Evaluate the Conduct a through evaluation of all Disease behaviours in individuals Containment operations societal, and effectiveness of Interventions implemented. for self protection. and other activities; pharmaceutical the measures used to Plan for use of collaborate with WHO and measures. update guidelines, pharmaceuticals the international protocols, and and vaccines. community as necessary. algorithms. Continuity of Healthcare Prepare the health Activate Implement contingency Rest, restock Evaluate the response of the Provisions system to scale up. Contingency plans. plans for health systems resources, revise health system to the pandemic at all levels. plans, and rebuild and share the lessons learned. Essential services. 8/30/2009 15

WHO Video for Pandemic Influenza Phases Video: "Pandemic influenza preparedness and response" 9/6/2009 15

EU Alert Levels in WHO Phase 6 EU alert level Description EU Alert Level One No confirmed human cases infected with the pandemic virus in any EU Member State EU Alert Level Two One or more confirmed human case(s) infected with the pandemic virus in any EU Member State EU Alert Level Three A confirmed outbreak (transmission) with the pandemic virus in any EU Member State EU Alert Level Four Widespread transmission in EU Member States 9/6/2009 16

Irish Alert Levels In WHO Phase 6 Irish Alert Level Description Irish Alert Level 1 Cases only outside Ireland (in a country or countries with or without extensive Irish travel/trade links Irish Alert Level 2 New virus isolated in Ireland (Announced June 11 2009) Irish Alert Level 3 Outbreak(s) in Ireland (not formally announced) Irish Alert Level 4 Widespread activity in Ireland Currently in Ireland “Alert Level 3” (but not formally announced) First Confirmed case In Dublin Ireland May 30th 2009 Announced April, 3, 2009 9/6/2009 17

Bio-event Disasters SEIRV Triage Model Categories • Susceptible • Exposed • Infectious • Removed • Vaccinated 9/6/2009 18

“Biological Triage” Mitigation High Transmissibility • Influenza Mitigation: Susceptible • Identify & treat primary infections Exposed Infectious • Preventative Goal: • Prevent and delay secondary Removed infections Vaccinated  Prevent and delay clustered in-country transmissions  Keeping in mind the severity of the influenza virus country by New ECDC “containment vs delayed” article country (High Transmissibility = Low or no containment therefore “delay” transmissions in WHO phase 4-6 ) According to WHO: Influenza A(H1N1) Secondary attack rate of 22-33% 9/6/2009 19 compared to 5-15% for seasonal influenza

Pandemic (H1N1) 2009 Epidemiology Five-year-old Edgar Hernandez, known as "patient zero" survived the earliest documented case of swine flu. “April 2 2009” 9/6/2009 20

Laboratory-confirmed cases of pandemic (H1N1) 2009 as officially reported to WHO by States Parties to the IHR (2005) as of 30th August 2009 Region Cumulative total as of 30th Aug 2009 Cases* Deaths WHO Regional Office for Africa (AFRO) 3872 11 WHO Regional Office for the Americas (AMRO) 116046 2234 WHO Regional Office for the Eastern Mediterranean (EMRO) 5031 21 WHO Regional Office for Europe (EURO) Over 46000 At least 104 WHO Regional Office for South-East Asia (SEARO) 19362 188 WHO Regional Office for the Western Pacific (WPRO) 63895 279 Total Over 254206 At least 2837 “Given that countries are no longer required to test and report individual cases, the number of cases reported actually understates the real number of cases” (WHO)

Pandemic (H1N1) 2009 Epidemiology Five-year-old Edgar Hernandez, known as "patient zero" survived the earliest documented case of swine flu. “April 2 2009” 9/6/2009 22

Pandemic (H1N1) 2009 Outbreak In Ireland as of 6th,September, 2009 Country Laboratory confirmed cases In-country Deaths of Pandemic Influenza Transmission A(H1N1) 2009 Virus Ireland 801 (HSE) 38+ 2 (Approx 2500-3500+ cases) Aug 7th ,16th 2009 (April 30 2009 1stcase) Northern 160 (HPA) unknown 1 Ireland (May 1 2009 1st case) Last Report Influenza Surveillance in July ,28, 2009 Ireland ‐ Weekly Update Influenza Week 35 2009 DOHC FAQ’s EU/EFTA 48,269 (ECDC) unknown 121 (Aug 24rth –30th 2009) Non EU 222,984+ 3,251 Global # 271,253+ 3,372 HPSC: “From Thursday July 16th GPs are moving to treat only certain categories of patients suspected of having influenza A(H1N1)v. GPs will decide, on the basis of a range of clinical and other features which patients need treatment. As most patients will have relatively mild symptoms, they will not need any antiviral medication and will recover by staying at home (to prevent spreading infection to others), drinking plenty of fluids and taking paracetamol regularly to relieve their symptoms.” ECDC: The number of confirmed cases reported is based on laboratory test results, except for the US. Depending on the national laboratory testing policies, the actual number of cases by country may therefore be higher. Several countries have now 9/6/2009 announced concentrating on mitigation measures and this usually implies focused laboratory testing. For these countries, the 23 reported numbers of cases presented in this report will severely underestimate the true incidence in the country and will not be comparable to countries still recommending laboratory tests of all suspected influenza cases.

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • Summary As of September,3rd,2009 • Based on the surveillance of laboratory confirmed cases of Pandemic (H1N1) 2009 virus – Total of 801 confirmed cases were notified in Ireland – 33.7 per 100,000 per population ( 88 new confirmed cases) – The median age of cases was 22 years (range: 0-82 years) and 84% were less than 35 years of age – Most cases in Ireland continue to be mild and 2 deaths has been reported Influenza Surveillance Total Confirmed Cases of ILI consultation Pandemic (H1N1) 2009 Week Pandemic (H1N1) 2009 Rate/100,000 Rate/100,000 (Deaths) Population Population of new Normal seasonal activity confirmed cases/week 17.8 per 100,000 30 217 37 per 100,000 5.1 per 100,000 31 365 35.3 per 100,000 3.1 per 100,000 32 513 (1) 33.1 per 100,000 12.1 per 100,000 33 619 (2) 38.8 per 100,000 14.6 per 100,000 34 713 (2) 35.7 per 100,000 16.8 per 100,000 35 801 (2) 33.7 per 100,000 18.9 per 1000,000 9/6/2009 24

Surveillance System: EU Surveillance Networks • Enter-net International Co-circulation of 2009 H1N1 and Seasonal Influenza • Eurosurveillance • European Surveillance System (TESSy) • European Antimicrobial Resistance Surveillance System (EARSS) • European Influenza Surveillance Network (formerly the European Influenza Surveillance Scheme • European Programme for Intervention Epidemiology Training (EPIET) • European Scientific Working Group on Influenza (ESWI) • FluNet Global Salm-Surv (GSS) • International Network of Paediatric Surveillance Units 9/6/2009 25

International Surveillance System • International • Europe • – The European Union United Kingdom – EU Public Health Eurosurveillance British Paediatric Surveillance Unit (BPSU) – World Health Organisation: Europe • Communicable Disease Surveillance Centre, (NI) • Worldwide – Australia: Communicable Diseases • Department of Health (UK) Australia • Department of Health, Social Services and – Australia: Immunise Australia Public Safety (NI) Programme • Faculty of Public Health Medicine (UK) – Canada: Health Canada • Health Promotion Agency (NI) – New Zealand: Ministry of Health, • Scottish Executive Health Department New Zealand • Welsh Assembly Government – USA: Centers for Disease Control – World Health Organisation: International 9/6/2009 • 26

Surveillance System: National Surveillance Institutes in Europe • Belgium: l'Institut scientifique de Santé • Netherlands: Rijksinstituut voor Publique Volksgezondheid en Milieu (RIVM) • Norway: Folkehelseinstituttet • Czech Republic: Centrum Epidemiologie a • Poland: Panstwowy Zaklad Higieny (PZH) Mikrobiologie (CEM) • Portugal: Direcção-Geral da Saúde • Denmark: Statens Serum Institut (SSI) • Slovak Republic: Úrad Verejného • Estonia: Tervisekaitseinspektsioon Zdravotnictva (UVZ) • Finland: Kansanterveyslaitos (KTL) • Slovenia: Inštitut za varovanje zdravja (IVZ) • Spain: Instituto de Salud Carlos III • France: Institut de Veille Sanitaire (InVS) • Sweden: Smittskyddsinstitutet (SMI) • Germany: Robert Koch Institut (RKI) • UK (England & Wales): Health Protection • Greece: Hellenic Center for Infectious Agency (HPA) Diseases Control (KEEL) • UK (Northern Ireland): Communicable Disease Surveillance Centre (CDSC) • Hungary: Országos Epidemiológiai Központ • UK (Scotland): Health Protection Scotland (OEK) (HPS) • Iceland: Landlæknir • U.S. Department of Health and Human • Italy: Istituto Superiore di Sanità (ISS) Services (DHHS) • Latvia: Sabiedribas veselibas agentura (SVA) • Luxembourg: Direction de la Sant 9/6/2009 27

Pandemic (H1N1) 2009 Surveillance Links Further information hyperlinks : International http://www.hse.ie/eng/ • CDC, US • http://www.dohc.ie • PAHO • http://www.who.int/en • ECDC • http://www.cdc.gov/swineflu/ • HPA, UK • http://www.ecdc.europa.eu/en/Pages/home.aspx • WHO • http://www.hpa.org.uk/ • PHAC Canada • http://www.nathnac.org/pro/swineflu.htm • http://www.phac-aspc.gc.ca/alert-alerte/h1n1/index- eng.php • Department of Education Further Irish Sites of Interest • Central Statistics Office Irish • Faculty of Public Health • Health Service Executive (HSE) Medicine, RCPI • Department of Health and Children • Health Research Board • Department of Foreign Affairs • Food Safety Promotion Board • Department of Agriculture • CIDR (must have login) • Irish College of General Practitioners (ICGP) • Department of Education 9/6/2009 28

Pandemic (H1N1) 2009 Surveillance in Ireland • Reporting of clinical data by sentinel GPs • Hospital Surveillance • Enhanced surveillance • Surveillance of absenteeism rates in sentinel schools • Mortality Surveillance • Regional influenza activity by HSE area • Surveillance in Containment Phase: – Pandemic Influenza A(H1N1) 09 Virus Pandemic Influenza Influenza Surveillance Weekly Surveillance Report A(H1N1) 09 Virus in Ireland July 20th – Infection 27th 2009 Weekly Surveillance • Surveillance in Mitigation phase: Report As of July, 18, 2009 • Weekly Influenza surveillance Report – Published every Thursday – Epi-Insight Monthly 9/6/2009 29

Pandemic (H1N1) 2009 Virus Surveillance in Ireland • Since the public health emergency was declared by WHO, HPSC and the HSE have implemented a number of surveillance initiatives to monitor the situation including: • Enhanced influenza A(H1N1) case based reporting on the Computerised Infectious Disease Reporting system (CIDR) • Contact tracing surveillance for contacts of influenza A(H1N1) cases • Expanded outbreak reporting of influenza and influenza-like illness on CIDR • An interim protocol on outbreak/cluster surveillance to detect early cases of influenza A(H1N1) • A protocol for surveillance of influenza-like illness in healthcare workers during Pandemic Phase 6. • Increased virological surveillance by the sentinel GP influenza surveillance system and recruitment of additional sentinel GPs • Expanded sentinel hospital influenza surveillance to capture information on the age breakdown of respiratory admissions Cited from Epi-insight • Sentinel paediatric hospital influenza surveillance systems have been implemented at two sites • Work is ongoing in the establishment of pilot sites for the sentinel surveillance of persons with influenza A(H1N1) who are admitted to intensive care units • Mortality surveillance has also been augmented with weekly monitoring of all cause mortality and deaths from pneumonia and influenza. HPSC will participate in a European mortality surveillance project (Euro MoMo) from early June 2009. Computerised Infectious Disease Reporting (CIDR) Adapted from Dr Jaon O'Donnell PTT From HPSC ICGP NRVL DPH/MOH Other Sentinel GP ILI consultations Hospital admissions GRO Mortality data Sentinel specimens School absenteeism HSE Influenza antiviral/vaccine uptake Non-Sentinel specimens Enhanced influenza surveillance GP Co-Ops ILI (Cluster) outbreaks Contact tracing International EISS, HPA, etc Influenza notification Health Protection Surveillance Centre (HPSC) European Influenza WHO Global Outbreak and Department of Public Health Weekly surveillance report Surveillance System (EISS) Alert Response Network and Children (GOARN) 30

Influenza Irelands Surveillance Systems • The role of HPSC as influenza surveillance co-ordinator is to: • Maintain and develop the current sentinel influenza surveillance network • Oversee enhancements as outlined e.g. year round surveillance, surveillance of hospitalised cases • Promote year round surveillance of influenza • Maintain close working relationship with the National Virus Reference Laboratory (NVRL) and the Irish College of General Practitioners (ICGP) 9/6/2009 31

Pandemic (H1N1) 2009 Irelands Surveillance Systems • World Health Organization “GOARN” • European Influenza Surveillance System (EISS) • Irish • The National Influenza Surveillance System • 1. Reporting of clinical data/influenza-like illness (ILI) by sentinel GPs • 2. Virological reporting (NVRL) • 3. Hospital surveillance comprising weekly data on total admissions, total Emergency Department (A&E) admissions and total respiratory admissions (upper respiratory tract infection, lower respiratory tract infection, pneumonia, asthma, chronic bronchitis, and exacerbations of chronic obstructive pulmonary disease) from sentinel hospitals • 4. Surveillance of absenteeism rates in sentinel schools • 5. Reports on outbreaks due to influenza or ILI • 6. Mortality data (weekly review of all cause and pneumonia and influenza registered deaths (uncoded)) from the General Registrar’s Office (GRO) • 7. Weekly regional influenza indices based on clinical activity, virological activity and outbreak activity. This is defined as no report, no activity, sporadic activity, localised activity, and widespread activity – Computerised Infectious Disease Reporting (CIDR) – Hot Line: • The Flu Information Line is available 24 hours a day and is your primary source of information on Influenza A(H1N1). • Freephone: 1800 94 11 00 9/6/2009 32

Computerised Infectious Disease Reporting (CIDR) Dissemination Pathway http://www.hpsc.ie/hpsc/CIDR/Presenta tions/File,1112,en.pdf 9/6/2009 33

The statutory requirement to notify all cases of Pandemic (H1N1) 2009 to the regional Director of Public Health/Medical Officer of Health (DPH/MOH) Under the Infectious Diseases (Amendment) (No.3) Regulations 2003 (SI No.707 of 2003) laboratory and clinical notification of swine influenza A (H1N1) is mandatory 9/6/2009 34

Pandemic (H1N1) 2009 Outbreak In The Republic of Ireland 2009 • Map of influenza activity by HSE area as of 3rd , September 2009 (n=801) Deaths - 2 Map week 35 HSE-North West - 66 HSE-North East- 93 HSE-Midlands - 28 HSE-West- 53 HSE-Midlands West- 65 Map week 33 Map week 34 HSE-South- 114 HSE-South East- 54 HSE-East – 328 Deaths - 2 Influenza Weekly Surveillance Report “Week 35” Please note one week lag time in reported cases!

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • Summary As of September ,3rd ,2009 • Based on the surveillance of laboratory confirmed cases of influenza A(H1N1)v – Total of 801 confirmed cases were notified in Ireland – 33.7 per 100,000 per population ( 88 new confirmed cases) – The median age of cases was 22 years (range: 0-82 years) and 84% were less than 35 years of age – Most cases in Ireland continue to be mild and 2 deaths has been reported Influenza Surveillance Total Confirmed Cases of ILI consultation Pandemic (H1N1) 2009 Week Pandemic (H1N1) 2009 Rate/100,000 Rate/100,000 (Deaths) Population Population of new Normal seasonal activity confirmed cases/week 17.8 per 100,000 30 217 37 per 100,000 5.1 per 100,000 31 365 35.3 per 100,000 3.1 per 100,000 32 513 (1) 33.1 per 100,000 12.1 per 100,000 33 619 (2) 38.8 per 100,000 14.6 per 100,000 34 713 (2) 35.7 per 100,000 16.8 per 100,000 35 801 (2) 33.7 per 100,000 18.9 per 1000,000 9/6/2009 36

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report Number of confirmed cases of Pandemic (H1N1) 2009 by week number, in Ireland as of 30th, August, 2009 (n=801) 160 Number of confirmed cases of 140 148 Pandemic (H1N1) 2009 131 120 100 107 93 80 78 88 60 51 40 37 16 35 20 4 9 1 0 0 0 1 1 0 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 Week Number 9/6/2009 37

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • ILI GP consultation rates per 100,000 population, baseline ILI threshold rate, and number of positive influenza specimens detected by the NVRL, by influenza week and season Normal seasonal activity 17.8 per 100,000 Pandemic (H1N1) 2009 is the dominate influenza virus circulating; in week 35, 100% of specimens positive for influenza were pandemic (H1N1) 2009 9/6/2009 38

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • Number of sentinel and non‐sentinel respiratory specimens and positive results, influenza week 35 and 34 2009 and Summer 2009 season to date Week 35 Week 34 9/6/2009 39

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • Pandemic (H1N1) 2009 confirmed cases (n=801) • 408 were female (50.9%%) • 386 were male (48.1%) • 7 unknown • Median age was 222 years (range: 0-82 years) • 84% of cases were less than 35 years of age • The highest age specific rate was observed in the 15-19 years age group • Number of confirmed cases of influenza A(H1N1)v and notification rate per 100,000 population by age group (years) 9/6/2009 40

Pandemic (H1N1) 2009 Hospitalizations and Severity of Illness • As of 30th September 2009 the number of • Pandemic (H1N1) 2009 clustered outbreaks: confirmed cases of pandemic (H1N1) 2009 • Total: 29 clustered outbreaks admitted to hospital by age group (years) and – 15 occurred in family settings sex (n=80) – 8 occurred in educational settings – 1 crèche • Forty-nine hospitalised cases have recovered or – 1 occurred in a community hospital/long-stay unit are recovering (73%) – 1 in a hotel • Twenty-five (43.8%) of the hospitalised cases – 1 at workplace had pre-existing clinical conditions – 1 involved travelling companions – 22 cases developed pneumonia – Location was not specified for one outbreak – 6 developed acute respiratory distress syndrome (ARDS) which 3 had pneumonia – 10 cases developed other respiratory problems – 1 developed otitis media – Acute renal failure and multi-organ failure was reported 9/6/2009 41

Pandemic (H1N1) 2009 Hospitalizations and Severity of Illness • 3rd September 2009 Update Summary: • 82 cases of confirmed pandemic (H1N1) 2009 have been hospitalised • Hospitalised cases (n=82) – 30 (40.0%) have an underlying condition putting them at increased risk of complications – Currently, 20 cases of confirmed pandemic (H1N1) 2009 remain hospitalised – 7 cases of confirmed pandemic (H1N1) 2009 have been admitted to ICU to date – 4 cases of confirmed pandemic (H1N1) 2009 currently remain in ICU – 2 patients with confirmed pandemic (H1N1) 2009 have died Currently Total Currently in ICU Total ICU cases Hospitalised Hospitalised 0-4 yrs 4 8 0 0 5-14 yrs 1 12 0 0 15-64 yrs 14 57 4 7 65+ 0 4 0 0 Total 20 82 4 7 9/6/2009 42

Pandemic (H1N1) 2009 Influenza Weekly Surveillance Report • No travel related report for week 34/35 • Week 33 report below! • Number of confirmed cases of influenza A(H1N1)v by mode of transmission and week 33 of notification (n=619) • 56% (n=206) were travel related (imported) • 7.4% (n=27) were contacts of an imported case (secondary import related) • 4.4% (n=16) were linked to a non‐imported case (tertiary indigenous) • 32.0% (n=117) had no history of travel and no known links to other confirmed cases (sporadic indigenous) • Mode of transmission was not reported for 253 (40.9%) pandemic (H1N1) 2009 cases 9/6/2009 43

Pandemic (H1N1) 2009 as of 6th Sept, 2009 Pandemic (H1N1) 2009 Confirmed Cases of Circulating Avian Pandemic (H1N1) Influenza H5N1 in 2009 (Deaths) Humans United States 45,771 (593) No activity Mexico 21,857 (199) No Activity Australia 35,474 (161) Sporadic Chile 12,194 (130) No activity Canada 12,127 (72) No activity United Kingdom 13,192 (70) No activity Thailand 11,585 (111) Sporadic Philippines 3,207 (28) Sporadic Argentina 8,240 (465) No activity Japan 5,022 (10) Sporadic Ireland 801+ (2) No activity (appox 2000-3500) 9/6/2009 44

MADRID – “Spain Became the First Country in Europe” With Pandemic (H1N1) 2009 • MADRID --In Catalonia Spain, officials confirmed the first European case of an infection in a person who had not (recently) travelled to Mexico, in a person whose girlfriend had done so, the second WHO region to experience transmission of this strain of H1N1 • As of June 15 2009 Europe reported its first death in Scotland in a 38 year old pregnant women – Had premature baby boy in June but the baby has died however he tested negative for Influenza A(H1N1) – 2nd death- An unnamed 73-year-who died on Saturday night after 15 days in June 14 2009 intensive care First and second death • As of June 27 2009, Europe has reported it 2nd death in Europe! – Girl aged 9 dies in Birmingham hospital – As of June 30 2009, Europe has reported its 3rd Death • A 19-year-old girl died of the H1N1 influenza Tuesday in Madrid June 27 2009 – The girl, of North African origin, who also suffered from asthma, was 28 weeks Third death in Europe! pregnant. Doctors performed a caesarean section on her on Monday due to the seriousness of her condition • 18 year old girl , from Templeboy, Co Sligo with underlining cystic fibrosis became the first Irish person to die after contracting pandemic June 30 2009 influenza H1N1v (Tallaght hospital) Fourth death in Europe! • 50 year old male from Dublin died at Beaumont hospital query underlined cardiac condition As of 4th ,Sept ,2009 … 120 deaths in Europe have occurred Aug 7/16 2009 United Kingdom (70) Netherlands- (2) Sweden (2) 1st and 2nd death in Ireland! Spain (23) Ireland – (2) Italy (1) Hungary (1) Malta – (2) Belgium – (1) Greece (2) France – (14 ) Norway (1) 45

Pandemic (H1N1) 2009 Europe's Geographical Spread by Date 9/6/2009 46

Pandemic (H1N1) 2009 Cumulative Epidemic Curve: Aug 6th 2009, 2009 Wikipedia: A semi-logarithmic chart of laboratory-confirmed Pandemic (H1N1) 2009 cases by date according to WHO reports 9/6/2009 47

ECDC Reported cumulative number of confirmed cases and of in-country transmission of Pandemic (H1N1) 2009 as of 9, Aug, 2009, 17:00 hours (CEST) in the EU and EFTA countries Last “Situation Report” 9/6/2009 48

Influenza A(H1N1)v Outside (EU) and EFTA ECDC Tables Aug, 9, 2009 9/6/2009 49

ECDC Daily Report Pandemic (H1N1) 2009 Report Reported number of confirmed pandemic influenza (H1N1) Reported number of new and cumulative confirmed fatal 2009 cases currently admitted to hospitals and ICU’s and pandemic influenza (H1N1) 2009 cumulative deaths among confirmed cases by country as of 4th cases by country as of 4th September 2009, 16:00 hours September 2009, in the EU and EFTA countries (CEST) outside of the EU/EFTA area Confirmed cases Deaths 9/6/2009 http://ecdc.europa.eu/en/healthtopics/Documents/090904_Influenza_AH1N1_Situation_Report_1700hrs.pdf 50

Number of Confirmed Deaths Among Pandemic (H1N1) 2009 Cases by Week of Notification • EU and EFTA countries week 25 to week 35 • World : Week 18 to week 35 9/6/2009 51

European Influenza Surveillance Network (EISN) Irish Summary Intensity: Medium Geographical Spread : Local http://ecdc.europa.eu/en/activities/surveillance/EISN/Newsletter/SUN_EISN_IN FL_Bulletin_2009week35.pdf 9/6/2009 52

Pandemic (H1N1) 2009 Americas Outbreak 2009 • As of 4th September 2009, a total of 120,653 confirmed cases have been notified in all 35 countries in the Americas Region. A total of 2,467 deaths have been reported among the confirmed cases in 22 countries of the Region. Update on the Qualitative Indicators for week 34 July , 17, 2009 Widespread Activity Trend Activity Intensity Activity Healthcare Impact • Geographical spread: refers to the number and distribution of sites reporting influenza activity • Trend of respiratory disease activity compared to the previous week: refers to changes in the level of respiratory disease activity compared with the previous week • Intensity of Acute Respiratory Disease in the Population: is an estimate of the proportion of the population with acute respiratory disease, covering the spectrum of disease from influenza‐like illness to pneumonia • Impact on Health‐Care Services: refers to the degree of disruption of health‐care services as a result of acute respiratory disease 9/6/2009 53 Regional Update. Pandemic (H1N1) 2009. (published on August 21, 2009)

Pandemic (H1N1) 2009 Outbreak In The United States 2009 The date of the onset of symptoms of the first confirmed case was 28 March 2009 in the United States. U.S. Human Cases of H1N1 Flu Infection 2009 US Swine Flu Summary: 43,771 confirmed cases (estimated 250,000) First Death Inside the US April 27, 2009 First Death of US Citizen May 5, 2009 As of Aug 30th , 2009, 9,079 hospitalizations and 593 deaths • 16 deaths in individuals 0-4 years • 93 deaths in individuals 5-24 years • 249 deaths in adults 25-49 years • 171 deaths in adults 50-64 years • 57 deaths in adults age 65 and older • 7 deaths with unknown age 9/6/2009 CDC is reporting every Fridays in “Fluview “Surveillance Report 54

Pandemic (H1N1) 2009 United States Outbreak • Influenza Viruses Isolated by Week 34 August 23-29, 2009 Week ending 2009 The dominate circulating strain in the U.S.A is Pandemic (H1N1) Influenza virus (97%) 9/6/2009 55

Pandemic (H1N1) 2009 México Outbreak 2009 As of 4th Sept 2009 (PAHO) Aguascalientes - 403 Hidalgo - 499 Morelos - 302 Querétaro - 456 Baja California - 395 Jalisco – 1,013 Nayarit - 268 Quintana Roo - 498 Baja California Sur - As of , 4th Sept 2009 79 Laboratory confirmed cases - 21,857 Deaths - 193 (199-ECDC) San Luis Potosí - 902 The majority (65.2%) of confirmed cases were in patients 5 to 29 years of age Campeche- 154 72.1% of all fatal cases in patients 20 to 54 years old. Sinaloa - 141 Regional Update Pandemic (H1N1) 2009 Chiapas – 2,899 (September 04, 2009 - 22 h GMT; 17 h EST) Sonora - 201 Chihuahua - 399 Tabasco – 1,222 Tamaulipas - 307 Coahuila - 33 Tlaxcala - 184 Colima - 213 Veracruz – 1,407 Durango- 169 Federal District - Nuevo León- 501 3,091 Yucatan – 1,992 Guanajuato - 354 Mexico State - 729 Oaxaca - 244 Guerrero – 1,013 Zacatecas - 721 Michoacán - 578 Puebla - 159 9/6/2009 Wiki:21,148 56 Individual regions #’s are days behind

Pandemic (H1N1) 2009 Outbreak in Canada • As of 4th Sept 2009 (week 34) a total of 12,127 + (CHICA) laboratory-confirmed cases of Pandemic (H1N1) 2009, including 1,454 hospitalizations, 283 cases admitted to an intensive care unit (ICU) and 72 deaths (4 Paeds), have been reported in Canada from all provinces and territories. July 16 2009 Canada will no longer be releasing individual confirmed cases of H1N1 flu virus three times weekly. Instead, the existing FluWatch surveillance program will be enhanced in order to give a more robust analysis of the national picture in Canada Yukon - 3 Nunavut – 496 Death - 1 North West Territories-29 Newfoundland - 101 British Columbia – 745 Deaths - 4 Prince Edward Island- 12 Alberta- 1,659 Death - 7 Nova Scotia – 580 Saskatchewan – 888 Death - 1 Deaths - 4 New Brunswick - 141 Manitoba - 886 Deaths - 7 Ontario – 4,053 Quebec- 2,506 Deaths - 23 Deaths - 25 9/6/2009 PHAC: FluWatch weekly report and bi-weekly report of deaths 57 Confirmed cases obtained from “CHICA”

Pandemic (H1N1) 2009 United Kingdom Outbreak According to HPA 13,192 Confirmed Cases and 70 deaths as of September,3rd,2009 National Protection Agency (HPA ) “Weekly National Influenza Report” •In week 35, 5000 new cases are estimated to have occurred (range 3000 – 12,000) Scotland- 1798 •The estimated number of new cases has decreased in all regions and age groups •Dominant virus remains Pandemic (H1N1) 2009 Death - 6 •348 new patients were hospitalised with suspected pandemic influenza corresponding to a rate of 0.7 per 100,000, a decrease from 0.8 per 100,000 in week 34 •Highest hospitalisation rate has consistently been in those aged under 5 years Northeast – 55 Deaths - 2 Northern Ireland – 160 Yorkshire and Humberside – 143 Deaths - 1 Deaths - 2 North West – 97 East Midlands – 147 Deaths - 1 Death - 1 East of England – 411 Wales – 118 Deaths - 15 Deaths - 1 London – 1,939 West Midlands – 2,582 Death - 22 Death - 8 South West – 198 South East – 598 Deaths - 2 Deaths - 1 9/6/2009 58 HPA Weekly National Influenza Report 03 September 2009 (Week 36)

Pandemic (H1N1) 2009 Australia Outbreak 2009 As of 6th September 2009 Week 33: 35,474+ Laboratory confirmed cases and 161 deaths Northern Territory – 1,377+ Hospitalizations 4,559 Death - 6 369 in hospital Queensland – 10,278+ 69 in ICU Death - 36 Western Australia – 3,692+ Death - 20 New South Wales – 4,699+ Deaths - 46 First case: 9 May 2009 Australian Capital Territory – 940+ Death - 2 South Australia – 6,358+ Death - 17 Tasmania – 225+ Victoria – 2,924+ Death - 6 Death -23 9/6/2009 59 (National H1N1 Influenza 09 Update 12 noon 6 September 2009)

Pandemic (H1N1) 2009 Southern Hemisphere Overview • Australia: As of September 6, 2009, Australia has 35,44 confirmed cases,4559 hospitalizations and 161 deaths. National influenza activity appears to be decreasing. Most jurisdictions have reported that Pandemic (H1N1) 2009 activity has peaked or has plateaued. ILI presentation rates to General Practitioners are below 2007 levels, and absenteeism rates have decreased. Indigenous Australians are approximately 5 times more likely than non-Indigenous Australians to be hospitalized for Pandemic (H1N1)2009. There are currently 369 people in hospital around Australia with pandemic (H1N1) 2009 and 69 of these are in Intensive Care Units. • New Zealand: As of September 4, 2009, the total number of confirmed cases in New Zealand is 3,145, 981 hospitalizations and 17 deaths. The number of ILI consultations continues to decrease, but is still higher than in previous years. Healthline calls continue to be about 20% above normal levels . New Zealand ICUs have reported that between 12 - 15% of patients admitted to hospital with pandemic influenza require treatment in an intensive care unit • Argentina: As of 4th Sept 2009, Argentina reports 8,240 confirmed cases of Pandemic (H1N1) 2009, a total of 6,584 cases of severe acute respiratory infection requiring hospitalization, and 465 Pandemic (H1N1)- associated deaths. Argentina has reported at high level of influenza activity for the past 3 weeks, with an estimated ILI rate of 14.1/10,000 population for epi week 31. • Brazil: As of 4th Sept 2009 Brazil has reported 6,592 confirmed cases, 657 deaths. Since August 28 1,386 new cases confirmed and 100 deaths • Chile: As of 4th Sept 2009, the number of laboratory-confirmed cases in Chile is 12,194 and 130 deaths. In week 33 ILI activity is reported as mild and decreased to 7.2 per 100,000 population. Of confirmed cases, 1,480 have presented with severe acute respiratory infection, representing a hospitalization rate of 8.7 cases per 100,000 population. Since epi week 28 the proportion of Pandemic (H1N1) 2009 relative to other respiratory viruses has declined to reach 4% of respiratory virus detections in week 33. In persons over 5 years old, Pandemic (H1N1) 2009 predominates (88% of isolates). • South Africa: As of August 31, South Africa reported a total of 5,841 laboratory-confirmed cases and 27 deaths from Pandemic (H1N1) 2009. Pandemic (H1N1) 2009 represents the majority of influenza virus detections. South Africa represents 93% of the cases reported to WHO from the African Region. 9/6/2009 60

Estimates of the Basic Reproductive Rate (R0) • There have already been several estimates of the basic reproductive rate/ratio (R0) which all lie between 1 and 2; the range 1.4 to 1.9 being most probable • Internationally as of July 29 2009 the (R0) Rate is 1.5 • The basic reproduction number is the mean number of secondary cases a typical single infected case will cause in a population with no immunity to the disease in the absence of interventions to control the infection. • It is often denoted (R0) . When (R0) < 1 the infection will die out in the long run (provided infection rates are constant); but if (R0) > 1 the infection will be able to spread in a population • See case study “How to they Do it” Pandemic (H1N1) 2009 Virus Estimates of the Basic Reproductive Rate in Mexico” 9/6/2009 61

Zoonosis Swine Influenza Virus (SIV) “Zoonotic diseases are those diseases transmitted between animals and people and thus compromising public health as well as endangering livelihoods by affecting their livestock.” 9/6/2009 62

Global Early Warning System for Major Animal Diseases, including Zoonoses (GLEWS) • The Global Early Warning System for Major Animal Diseases, including Zoonoses (GLEWS) is a joint FAO, World Organisation for Animal Health (OIE) and WHO initiative to improve the early warning capacity to animal disease threats for the benefit of the international community • Certain animal health events with potential public health implications are included in the scope of the International Health Regulations (2005) (IHR(2005)) • Intersectoral collaboration, including between the veterinary, food safety and public health sectors is needed to effectively address the prevention of zoonotic diseases 9/6/2009 63

(GLEWS) Zoonotic and Non-Zoonotic Diseases • Zoonotic • Non zoonotic • Anthrax • African Swine Fever (ASF) • Bovine Spongiform Encephalopathy (BSE) • Classical Swine Fever (CSF) • Brucellosis (B. melitensis) • Contagious Bovine Pleuropneumonia (CBPP)* • Crimean Congo Hemorrhagic Fever • Foot and Mouth Disease (FMD)* • Ebola Virus • Peste des Petits Ruminants (PPR) • Foodborne diseases • Rinderpest – Stomatitis/Enteritis • Highly Pathogenic Avian Influenza (HPAI) • Japanese Encephalitis • Marburg Hemorrhagic Fever • New World Screwworm • Nipah Virus • Old World Screwworm WHO States : • Q Fever GLEWS is a joint system that builds on the added value of • Rabies combining and coordinating the alert mechanisms of FAO, • Rift Valley Fever* (RVF) OIE and WHO for the international community and stakeholders to assist in prediction, prevention and control of • Sheep Pox*/Goat Pox animal disease threats, including zoonoses, through sharing • Tularemia of information, epidemiological analysis and contribute to • Venezuelan Equine Encephalomyelitis joint field missions to assess and control the outbreak. • West Nile Virus 9/6/2009 64

Irelands Governmental Lead Agencies, Groups and Committees Emergency/Incident Type Lead Lead Response Principal Other Potential Remarks Government Agency as per Support Support Roles Department Framework Role Animal Infectious Diseases DAFF DF (DOD) Local Authorities HSE role relates Diseases (Animal) HSE (DEHLG) to zoonotic AGS (DJELR) diseases; DFA infectious animal CD (DOD) diseases with a DTRANS human health (IRCG/MSO/Shipping) dimension DAST • Strategic Emergency Planning Guidance – Lead, Principal and Other Support Roles: • DAFF (Department of Agriculture Fisheries & Food) • DEHLG (Department of the Environment Heritage & Local Government) • DOD (Department of Defence) • HSE (Health Service Executive) • DTRANS (Department of Transport) • IRCG (Irish Coast Guard) • MSO (Marine Service Office) • DAST (Department of Arts, Sport & Tourism) 9/6/2009 65

Swine Influenza (SIV) Outbreak History Year History of Swine Influenza 1918 Swine influenza H1N1 described in north central USA, Hungary, and China. May have been cause of human pandemic , which resulted in 20-40 million human deaths 1930 Shope isolated influenza virus from pigs The prototype classic swine influenza H1N1 strain (A/Swine/ Iowa/30) transmitted experimentally to pigs 1941 Recognised in Europe and disappeared 1970 Transmission of human H3N2 virus to pigs. Avian like H3N2 in pigs in Asia 1976 United Sates/New Jersey Virus enzootic to US swine herds since or before 1930 – One Adult with Severe Pneumonia 1979 Introduction of whole H1N1 virus from birds to pigs. Antigenically distinguishable from classical strains Still circulating today (2002) 1984 Reassortment between human H3N2 and avian H1N1 in swine resulting in reassortant H3N2 virus with avian internal gene segments H3N2 strains first associated with respiratory epizootics Still circulating today(2002) 1986 Classical H1N1 reappears in UK, similar to classical H1N1 in continental Europe 1987 Reassortant H3N2 associated with respiratory epizootics in UK Related to A/Port Chalmers/73 (H3N2) 1989 Avian like swine H1N1 is dominant and widespread in Europe 1992-1993 Avian like H1N1 strains widespread in UK 1993 Infection of children with reassortant H3N2 virus from pigs and isolation of avian like swine H1N1 virus from a pneumonia patient in the Netherlands 1994 H1N2 first isolated in pigs in UK, and later also in Belgium. Human avian reassortant virus 1992-1998 H3N1 (H3 human, N1 swine) and H1N7 (H1 human, N7 equine) also occurred in swine in the UK but failed to spread 1998 H9N2 in pigs and humans in Asia Apparently an avian virus that has adapted to pigs 1998 For the first time, H3N2 viruses cause severe disease in N. America. Viruses are triple (avian human classical swine) reassortants, distinct from earlier strains and European strains H1N2 identical to H3N2, but with H1HA from classical swine H1N1, also isolated 1999 Single case of isolation of avian H4N6 from pigs with pneumonia in Canada 2002 Current situation in Europe: avian like H1N1, and reassortant human like H3N2 and H1N2. In North America: classical swine H1N1, triple reassortant H3N2 2005-2009 11 sporadic cases of infection in humans with triple-reassortant swine influenza A H1 (See Genetic Components of Triple-Reassortant Swine Influenza A (H1) 2009 6 outbreaks of Pandemic (H1N1) 2009 have been identified in swine herds (Canada (2), Australia (3), Argentina (2) OIE Reports; Australia (31 07 2009 Confirmed in pigs) http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8358 Canada (01/05/2009 Confirmed in pigs) http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8180 Argentina (21/07/2009 Confirmed in pigs) http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8321 66

Swine Influenza A (Hsw1N1) Past Outbreak in United States • 1976 U.S. outbreak • In early 1976, the novel A/New Jersey/76 (Hsw1N1) influenza virus caused severe respiratory illness in 13 soldiers with 1 death at Fort Dix, New Jersey President Ford A/Victoria/75 (H3N2) spread simultaneously, also receives swine caused illness, and persisted until March flu vaccination • 230 soldiers were infected with the A/New Jersey virus • Vaccine Controversy; • 20-40 million vaccinated in US – Overall, there were about 500 cases of Guillain-Barré syndrome (GBS), resulting in death from severe pulmonary complications for 25 people, according to Dr. P. Haber – “Nachamkin et al (2008) found that inoculation of the 1976 swine flu vaccine, as well as the 1991-1992 and 2004-2005 influenza vaccines, Video from 1976 into mice prompted production of antibodies to antiganglioside (anti- Swine Influenza GM1), which are associated with the development of GBS. They proposed that further research regarding influenza vaccine Outbreak components is warranted to determine how these components elicit 9/6/2009 antiganglioside effects” (Source E-medicne) 67

Genetic Components of Triple-Reassortant Swine Influenza A (H1) • Triple-Reassortant Swine Influenza A (H1) Viruses Isolated from 11 Patients between December 2005 and February 2009 in the United States Triple-Reassortment Swine H1N1 Triple-Reassorment Swine Influenza Virus H1N2 Influenza Virus (Pts 1-6 and 8-11) (Pt 7 2009) Note Pt 8 visited a Pig Fair (genetic ressortment H1N2) PB2 PB2 PB1 PB1 PA PA HA HA NP NP NA NA M M NS NS http://content.nejm. org/cgi/reprint/NEJM oa0903812.pdf Triple -Reassortment Classical swine, North American Lineage Avian, North American Lineage Human (Seasonal )H3N2 9/6/2009 Human (Seasonal )H1N1 68

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • 11-MAY-2009 • Canadian Food Inspection Agency, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada • Collection date= 2009 • Organism : Influenza A virus (A/swine/Alberta/OTH-33-8/2009(H1N1) • Host = Swine • Embryonated chicken eggs passage 1CE-3dpi • Influenza A virus (A/swine/Alberta/OTH-33-8/2009(H1N1))segment 6 neuraminidase (NA) gene

Zoonosis Swine Influenza Virus (SIV) • Two types of virus have been isolated in Ireland : 1. H1N1 was isolated for the first time in November 1991 – The H1N1 isolated in Ireland, is different from the strains circulating in Europe and elsewhere, and probably represents a separate introduction of an avian strain into Irish pigs. It is serologically related to Weybridge 79 and OMS/2899/82 2. H3N2 was isolated for the first time in June 1993 – The H3N2 virus isolated is serologically related to OMS/3633/84 • Existence of H1N2 in Irish pigs has so far been scantly detected by % of seropositive sows (HI), 2002-03 *SIV subtype isolated in Ireland revealed the following: – Ireland – H1N1: 17.8* The novel A/H1N1 Influenza virus at the interface between humans and animals Swine influenza virus. Colorized – transmission electron micrograph H3N2: 4.2* What needs to be done in Europe? Brussels, 9 June 2009 (37,800X) of the A/New Jersey/76 (Hsw1N1) virus under plate magnification. Image taken during the virus' first – H1N2: 0.6 developmental passage through a chicken egg. Courtesy of the CDC/Dr. E. Palmer; R.E. Bates. 9/6/2009 70

Swine Influenza in Pigs Virus Subtypes • Influenza A was first recognized as a clinical illness in pigs in 1918, which coincided with the 1918-1919 influenza pandemic in humans • H1N1 influenza A virus was first isolated from pigs in the United States in 1930 • H1N2 viruses that resulted from reassortant between the triple reassortant H3N2 viruses and classical H1N1 swine viruses have been isolated occasionally in the United States • Avian H4N6 virus was recognized in pigs in Canada in 1999, but spread beyond the original farm of detection was not identified • A novel H3N1 influenza virus was isolated from pigs in the United States in the mid 2000s; this virus may have risen from reassortment of an H3N2 turkey isolate, a human H1N1 isolate, and currently circulating swine influenza viruses 9/6/2009 71

Swine Influenza (SIV) Signs and Symptoms In Swine • Symptoms of infected pigs include: – Fever (102-106°F) – Depression – Coughing (barking) – Sneezing – Difficulty breathing – Red or inflamed eyes – Lack of appetite – Discharge from the nose or eyes – Reduced fertility or abortion (boars and sows) – Mortality up to 15% 9/6/2009 72

Swine Influenza (SIV) Differential Diagnosis In Swine • The following diseases must be considered in the differential diagnosis: – Aujeszky's disease – Atrophic rhinitis – Enzootic (mycoplasmal) pneumonia – Actinobacillus pleuropneumoniae • (serotype 1-2-4-7-9-11, serotype 2, serotype 1-9-11 or serotype 4-7) – Bacterial pneumonia due to Pasteurella or Haemophilus spp. 9/6/2009 73

Swine Influenza (SIV) Porcine Diagnostic • Veterinary diagnostic kits: • Influenza A Antibody Competition ELISA kit • Influenza A Antigen Capture Kit • The kit detects antibodies directed against the A nucleoprotein in a wide range of species (avian, porcine, equine), including wild and zoo animals. 9/6/2009 74

Swine Influenza (SIV) Post-mortem findings In Swine • Post-mortem findings include: • The lesions are confined to the respiratory system and are not very specific. • Hyperaemic of the mucosa of the respiratory tract • Excess production of mucus • Atelectasis and emphysema of the cardiac and apical lobes of the lungs, • Enlarged bronchial and mediastinal lymph nodes • In fatal cases there may be an acute interstitial pneumonia “An overview on swine influenza” ptt Pictures Normal Normal Normal Lungs Infiltration of Desquamation of Abnormal Lungs neutrophils epithelial cells Normal Lungs 9/6/2009 75

Swine Influenza (SIV) Examples of Vaccines For Porcine! • Schering-Plough Animal Health Corporation: MaxiVac Excells • Novartis : PneumoSTAR® SIV Swine Vaccine • Pfizer Animal Health: FluSure vaccine 9/6/2009 76

Swine Influenza (SIV) European Vaccine List Name Virus strains Type Antigenic dose (company) Gripovac A/New Jersey/8/76 (H1N1) split H1N1 : ≥ 1,7 HI units (Merial) A/Port Chalmers/1/73 (H3N2) H3N2 : ≥ 2,2 HI units Suvaxyn Flu A/sw/Netherlands/25/80 (H1N1) whole virus H1N1 : 4 μg HA (Fort Dodge) A/Port Chalmers/1/73 (H3N2) H3N2 : 4 μg HA Gripork A/sw/Ollost/84 (H1N1) whole virus H1N1 : 3 x 107 EID50 H3N2 : 2,5 x 107 EID50 (Hipra) A/Port Chalmers/1/73 (H3N2) Respiporc Flu A/sw/Belgium/230/92 (H1N1) whole virus H1N1 : ≥ 256 HA units H3N2 : ≥ 256 HA units (IDT) A/sw/Belgium/220/92 (H3N2) Respiporc Flu3 A/sw/Haselunne/2617/03 (H1N1) whole virus H1N1 : ≥107 TCID50 A/sw/Bakum/1769/03 (H3N2) (IDT) A/sw/Bakum/1832/00 (H1N2) H3N2 : ≥107 TCID50 H1N2 : ≥107 TCID50 Slide List From Prof. Kristien Van Reeth Laboratory of Virology, Faculty of Veterinary Medicine “An overview on swine influenza” ptt 9/6/2009 77

National Biosecurity Importation of Swine In Ireland Directives • Swine- are prohibited to be imported from non-EU countries, except in compliance with Directive 72/462/EEC. • Licence issued in accordance with the Importation of Livestock Orders, 1970 to 1992 (S.I. No. 296 of 1970 and S.I. 298 of 1992). 9/6/2009 78

Pandemic (H1N1) 2009 Food Safety of Pork “INFOSAN” • Paris, 7 May 2009 • Joint FAO/WHO/OIE Statement on influenza A(H1N1) and the safety of pork • Influenza viruses are not known to be transmissible to people through eating processed pork or other food products derived from pigs. • Heat treatments commonly used in cooking meat (e.g. 70°C/160°F core temperature) will readily inactivate any viruses potentially present in raw meat products. Authorities and consumers should ensure that meat from sick pigs or pigs found dead are not processed or used for human consumption under any 9/6/2009 circumstances.! 79

Pandemic (H1N1) 2009 Prevention Department of Agriculture and Food and Fisheries (DAFF) • Agriculture and Food and fisheries (DAFF) will institute biosecurity measures • These control measures focus on animal health issues and aim to prevent any further spread of the disease among animals 9/6/2009 80

Irish Biosecurity Measures For Pig Farms: • Normal biosecurity measures on pig farms Include: • Limit the access to essential personnel (farm employees, veterinarians and essential service people) • Implement policies that prevent employees who present signs of flu-like illness from having contact with the pigs or other people on the holding • Prevent access of international visitors or people who have recently returned from international travel, particularly from swine influenza affected regions, into your holding • Implement a shower-in/shower-out procedure and the use of farm- specific clothing and footwear for employees entering the holding • At minimum, employees should don farm footwear and completely wash hands and arms before having contact with the pigs • Enforce heightened personal hygiene practices including frequent hand washing for all people in contact with pigs 9/6/2009 81

Biosecurity On Pig Farms $ Profits $ QUALITY ASSURANCE REDUCED MEDICATION REDUCED MORTALITY IMPROVED REDUCED ZOONOSIS REDUCED DISEASE PERFORMANCE BIOSECURITY 9/6/2009 82

Swine Influenza Virus (SIV) Transmission • Swine diseases can be spread in a number of ways, including: • Through diseased swine or healthy swine incubating disease • Through animals other than swine (farm animals, pets, wild birds and other wildlife, vermin and insects) • On the clothing and shoes of visitors and employees moving from farm-to-farm • In contaminated feed, water, bedding and soil • From the carcasses of dead animals • On contaminated farm equipment and vehicles • In airborne particles and dust blown by the wind An Egyptian policeman wears a mask as he stands guard in front of a pick up truck full of pigs at the main slaughterhouse in Cairo April 30, 2009 9/6/2009 83

Zoonosis Swine Influenza Virus (SIV) How Can Pigs Be protected? • The following actions can potentially prevent swine influenza: • Vaccinating animals • Ensuring farm workers maintain good hygiene • Following strict biosecurity practices • Providing adequate ventilation in barns • Identifying and segregating sick animals as early as possible 9/6/2009 84

Limit the Risk of Transmission SIV On Pig Farms 1. Decreasing the spread of SIV includes: 2. Traffic control 3. Isolation 4. Sanitation 5. Herd health management 6. Program maintenance 7. Ensue Personal Protection Equipment(PPE) onsite and an active fit testing program 8. Application of HACCP (Hazard Analysis of Critical Control Points) 9/6/2009 85

Swine Influenza Virus (SIV) Traffic control: • Traffic control: • Anyone exhibiting signs of respiratory illness should avoid contact with animals • Workers in swine facilities who have been exposed to influenza or someone diagnosed with influenza should avoid contact with animals until they have been checked by a healthcare worker • Avoid contact with swine outside regular employment • Control and restrict visitors' access to the herd • Require all visitors to wear clean boots, clothing and gloves and wash hands thoroughly on entry and exit • Prevent other animals from coming into contact with the herd • Maintain records of the movement of people, animals and equipment on and off the premises 9/6/2009 86

Swine Influenza Virus (SIV) Isolation: • Isolation: • Only obtain new animals from reputable sources and limit the frequency of introducing new pigs to the herd • House newborn, weaned, feeder, and breeding pigs separately • Move pigs in groups during each production stage, in an all-in-all-out manner 9/6/2009 87

Swine Influenza Virus (SIV) Sanitation: • Sanitation: • Routinely clean and disinfect buildings, barns, equipment, clothing and footwear • Designate a cleaning area for vehicles and equipment • Promptly dispose of dead pigs in a manner that minimizes the chance of spread of any disease • Implement a manure management program • Avoid borrowing equipment and vehicles from other farms 9/6/2009 88

Swine Influenza Virus (SIV) Herd Health Management: • Herd health management: • Monitor herd health daily and employ veterinary services • Uniquely identify all groups of animals for traceability purposes (where they came from and where they are sold to) • In consultation with a veterinarian, consider vaccinating animals • Isolate sick pigs and immediately report any signs of illness to your veterinarian or the nearest Department of Agriculture office A Litter-Bed Pigpen for Breeding and Growing-Finishing Pigs. 9/6/2009 89

Swine Influenza Virus (SIV) Program Maintenance: • Program maintenance: • Train all staff on your biosecurity program and monitor its effectiveness • Be aware of any diseases in your area and adjust your biosecurity program accordingly • Recommend farm workers discuss an annual flu vaccination with their doctor. – Vaccination may reduce the amounts of virus shed if infected during human influenza outbreaks, and limit the potential for human influenza virus infection of pigs. Full View of the The effectiveness of current human Litter-Bed Pig vaccines against this new strain is not known at this time Farm 9/6/2009 90

Hazard Analysis of Critical Control Points (HACCP) On PIG Farms • Application of HACCP (Hazard Analysis of Critical Control Points) procedures will help to identify areas of greatest risk to the business and allow for development of preventative strategies 9/6/2009 91

A General Biosecurity Checklist For Swine 9/6/2009 92

Veterinary Surveillance • This disease is a scheduled and notifiable disease in Ireland (Class B) • Porcine surveillance: The Department of Agriculture and Food and Fisheries (DAFF) (in collaboration with the porcine industry undertakes active and passive surveillance for porcine • Notification procedures is agreed between the department of Agriculture and Food and Fisheries the HSE in the event of Influenza being identified or highly suspected from porcine 9/6/2009 93

Swine Influenza Virus (SIV) Pharmacovigilance for Veterinarians • EU Veterinary Suspected Adverse Reaction form for Veterinary and Health Professionals 9/6/2009 94

Swine Influenza Virus (SIV) Preplanning for Veterinarians Visits: • The veterinarians should: • Prepare and plan the visit by Veterinarians Porcine log Book 2009 contacting the producer beforehand • Park in designated areas or as far as possible from animals • Keep a log book of farms visited 9/6/2009 95

Swine Influenza Virus (SIV) Interim Recommendations For Veterinarians: • Use appropriate personal protective equipment: – FFP 2-3 respirator masks, gloves, impermeable coveralls, protective clothing and footwear and eye protection • Wash hands thoroughly after handling animals • Leave as you arrived and clean and sanitize vehicles and equipment • Dispose of protective equipment in a safe manner: – either leave it on the farm to be appropriately disposed or – remove it and place it in “contaminated materials” containers for transport to the office • Prioritize work by attending low-risk jobs first and then observe animals for concerns • Avoid or minimize contact with manure storage, feed supplies, and water supplies • Until more is known about how this illness affects swine, if swine influenza is suspected – do not travel to another swine farm for 48 hours 9/6/2009 96

Swine Influenza Virus (SIV) Personnel Protection • On arrival at a site, personnel should: • Disinfect footwear in foot-bath • Put on washable or disposable protective clothing (footwear and overalls) • Wash hands • Before departure personnel should: • Disinfect footwear and protective clothing (or leave on site if disposable) • Wash hands • Contacts who work on pig farms should remain off work for 7 days as soon as diagnosis is suspected! 9/6/2009 97

Veterinarians Donning and Doffing PPE 9/6/2009 98

Veterinarians Donning and Doffing PPE (HPSC Resource) 9/6/2009 99

Department of Agriculture Local District Veterinary Offices (DVO) COUNTY ADDRESS TELEPHONE Carlow Athy Road, Carlow 059 9170022 Cavan Farnham St., Cavan 049 4368200 Clare Government Offices, Kilrush Road, Ennis, Co. Clare 065 6866042 Cork North Hibernian House, 80A South Mall, Cork 01 4149900 Cork Central Hibernian House, 80A South Mall, Cork 01 4149900 Cork West Darrara, Clonakilty Co. Cork 023 36200 Donegal Meeting House St, Raphoe, Co. Donegal 074 9145298 Dublin/ St John’s House, High St, Tallaght, Co. Dublin 01 4149900 Wicklow East Galway Dockgate Building, Merchants Rd., Galway 091 507600 Kerry Spa Road, Tralee, Co. Kerry 066 7145052 Kildare/ Poplar House, Poplar Square, Naas, Co. Kildare 045 873035 Wicklow West Kilkenny Hebron Road, Kilkenny 056 7772400 Laois Abbeyleix Road, PortLaoise, Co. Laois 057 8674400 Leitrim Cranmore Road, Sligo 071 9682000 Limerick Houston Hall, Ballycummin Avenue, 061 500900 Raheen Industrial Estate, Raheen, Co. Limerick Longford Ballinalee Road, Longford 043 50020 Louth North Quay, Drogheda, Co. Louth 041 9838933 Mayo Michael Davitt House, Castlebar, Co Mayo 094 9035300 Meath Athlumney, Kilcairn, Navan, Co Meath 046 9082900 Monaghan Main Street, Ballybay, Co. Monaghan 042 9748800 Offaly Clonminch, Tullamore, Co. Offaly 057 9346037 Roscommon Convent Road, Roscommon 090 6630100 Sligo Cranmore Road, Sligo 071 9142023 Tipperary North St Conlon’s Road, Nenagh, Co. Tipperary 067 50014 Tipperary South Government Offices, Davis Street, Tipperary 062 80100 Waterford Govt. Offices, The Glen, Co. Waterford 051 301700 Westmeath Bellview, Dublin Road, Mullingar, Co. Westmeath 044 9339300 Wexford Vinegar Hill Lane, Enniscorthy, Co Wexford 053 9242008 9/6/2009 100

EU Possible Quarantine Zones for Infected Pandemic Influenza A(H1N1) 09 Virus on Pig Farms Surveillance zones Surveillance zone (minimum of 10 km radius from the infected premises) Inplace for 30 days Protection Zone Quarantined Pig Farm Restricted zone (minimum of 1 -3 km radius from the infected premises) Controls must be kept in place for at least 21 days Infected Premises Restricted Zone Contaminated Porcine Farm There are no controls on people visiting the Zone Zone A Adapted from EU Quarantine for Avian Flu DAFF:Information on Avian Influenza Control Measures Buffer Zone 9/6/2009 101 Zone B

Risk vs. Benefit Analysis for Decontamination Decontamination is defined as : What are the outcomes of “The process of removing or neutralising a hazard from the environment, property or life form. Its objectives are to prevent further harm and optimise the chance for natural stabilization? full clinical recovery or restoration of the object exposed to the contaminant”. Yes Can I change the outcomes No Do nothing except protect of natural stabilization by exposures! the intervention? What are the cost of the Risk intervention in terms of risk EXCEEDS Do nothing except protect versus benefit? benefit exposures! Benefit “Decontamination Process” EXCEEDS Refers to removal of clothing, neutralization of contaminate, verification of contaminate neutralization, and isolation of all contaminated waste. benefit Engage in intervention operations as long as the 9/6/2009 benefit exceeds the risk 102

Quarantine Zones for Infected Pandemic (H1N1) 2009 Virus Pig Farms Agriculture and Food (DAF) will institute biosecurity measures . These control measures focus on animal health issues and aim to prevent any further spread of the disease among animals. Pending confirmation of the outbreak, if deemed necessary, all the porcine in the holding may be culled and destroyed. • Zone A : Infected premises • Buffer Zone: Surveillance zone • Risk vs. Benefit Analysis • The Surveillance Zone must stay in place for at least 30 days after the preliminary cleaning and disinfection of the infected • The Protection Zone must stay in place for at least 21 premises has been carried out. days after the preliminary cleaning and disinfection of • Identification of all porcine holdings the infected premises has been carried out, and then the • Prohibition on porcine fairs, markets, shows or other Zone becomes part of the Surveillance Zone gatherings • Killing and disposal of all porcine • Prohibition on the release of porcine, porcine products • Cleaning and disinfection of the premises Checkpoints will be • Destruction or treatment of manure, slurry and bedding put in place to control movements of • Tracing and destruction of porcine meat and carcasses vehicles transporting porcine or porcine produced during risk period related products • Epidemiological investigation and tracing of high-risk into/out of the Zones. contacts • Prohibition on porcine entering or leaving • Controls on people, vehicles and other things entering or leaving • Zone B: Free from Disease • Controls on re-stocking • A Further Restricted Zone may be declared outside the Surveillance Zone if this is considered necessary to control the disease. The measures to be applied in this Zone will be determined depending on a risk assessment 9/6/2009 carried out at the time. 103

Maximum Decontamination Infected Premises Footbath Layout Level C & D Protection Boot Cover Tape & (PPE) Reduction Outer Glove Removal Glove Wash Segregated Removal (Hypothetical example ) Equipment Stripper/ 6 5 4 3 2 1 Drop Bagger Boot Cover Boot Cover & Removal Glove Rinse Zone A 7 Suit/Safety Boot Wash Canister or 9 8 Suit/Safety Boot Rinse Mask Change and Redress - Boot Cover/ Outer Gloves 10 Safety Boot Removal 11 Splash Suit Removal CONTAMINATION 12 Inner Glove Wash REDUCTION The contamination hazards at hazardous sites Inner Glove Rinse vary greatly, the methods of decontamination ZONE 13 may be adjusted by omitting, adding, or changing the stations identified to reflect the 14 Face Piece Removal contamination hazards at a site! 15 Inner Glove Removal These figures are adapted from the, NIOSH/OSHA/USCG/EPA Occupational Safety and Health Guidance Manual for 16 Inner Clothing Removal Hazardous Waste Site Activities. CONTAMINATION CONTROL LINE SUPPORT Dryer/ 17 18 Field 9/6/2009 Dresser 104 ZONE Wash

Minimum WIND DIRECTION Decontamination Layout 20 Levels C & D Protection Redress: Boot Covers and Outer Gloves Zone A Decon 20 Solution Tank Change-Over Point (If needed) Infected Premises Remove Water Boots/Gloves and Decon Outer Outer Equipment Garments Garments Drop (For Disposal Remove and Off Site Boot Covers Decontamination) and Outer Gloves Footbath Plastic Sheet Can Zone A (10 gallon) Remove SCBA (If needed) Contamination Reduction Corridor 9/6/2009 105

Basic Personnel Decontamination Vehicle decon “Contamination Reduction Corridor” Setup Vehicle decon Decon Water Solution Inner Washer Rinser Stripper Zone A Equipment glove Drop bagger removal Zone Contaminated Porcine Farm Entry Wash Rinse Can PPE Removal Exit (10 gallon Support Footbath Can Can Can Zone A 10 gallon 10 gallon 10 gallon Footbath if no Decon pools CRC setup Storage and Garbage Plastic (Tarp or Visqueen) Barrier tape and pylons Contamination Reduction Corridor 9/6/2009 106

Vehicle Decontamination • Only allow essential vehicles onto the site. Staff, service vehicles etc. should be parked outside the perimeter. Insist that all vehicles that have to enter the site have been cleaned and disinfected beforehand • Vehicle cleaning and disinfection: • On arrival at the farm, wheels, wheel arches, outside and underside must be disinfected • Before leaving the farm, wheels, wheel arches, outside and A worker spraying disinfectant at a vehicle at underside must be washed and disinfected, ensuring that the the entrance of a turkey surfaces are visibly dry plant south of Santiago, Chile • Wash and disinfect all surfaces which may have come into contaminated material, such as: – Wheels, wheel arches, outside and underside – Trailer – Equipment (e.g. trolleys, crates, modules, delivery pipes, sheeting, covers) – Wipe areas of the driver’s cab that may have been contaminated, with disinfectant – Drivers should avoid contact with porcine or other porcine on premises outside the infected area for at least 3 days (72 hours) A list of approved disinfectants can be found at: http://www.agriculture.gov.ie 9/6/2009 107

Pandemic influenza (H1N1) Turkeys in Chile has Raised Fears • The H1N1 flu outbreak in turkeys in Chile was found in two farms in the Valparaiso region, 160km west of Santiago • The Chilean authorities have established a temporary quarantine on August 13th 2009 and decided to allow the infected birds to recover rather than culling them • The FAO called for better monitoring of the health of animals and for farms to follow good farming practice guidelines, 'including protecting farm workers if animals are sick and not allowing sick workers near animals‘ • Consumption of ill turkeys remains a concern but “We call on the public to consume turkey products with confidence,” a SAG statement said. • OIE weekly reports: • Chile (Confirmed in turkeys) • http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8404 • Australia (31 07 2009 Confirmed in pigs) • http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8358 • Canada (01/05/2009 Confirmed in pigs) • http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8180 • Argentina (21/07/2009 Confirmed in pigs) • http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8321 A worker spraying disinfectant at a vehicle at the entrance of a turkey plant south of Santiago, Chile 9/6/2009 http://www.recombinomics.com/News/07180901/H1N1_Swine_BA.html 108 http://www.oie.int/wahis/public.php?page=single_report&pop=1&reportid=8404

Food Safety Strategy for Ireland “National Control Plan 2007” 9/6/2009 109

Swine Influenza Virus (SIV) and Pandemic (H1N1) 2009 Swine Influenza Virus (SIV) Pandemic (H1N1) 2009 Influenza Virus • Swine influenza is • The Influenza Virus contains commonly transmitted genes from pig, bird and through direct contact or human influenza viruses, in close proximity with pigs. a combination that has never been observed before Secondary cases following anywhere in the world human-to-human • 2009 Quadruple transmission have been reassortment of three reported in the past but viruses—a human virus, an they have been very rare avian virus , and 2 porcine • 1998 Triple reassortment viruses 9/6/2009 110

Phylogenetic Comparison To Other Negative-sense RNA Viruses • Influenza strains are subtype A, B, or C • Based on the relatedness of the matrix (M1) and nucleoprotein (NP) antigens 9/6/2009 111

Pandemic (H1N1) 2009 “Influenza A Virus” Microbiology • Influenza A viruses are negative-sense single-stranded RNA viruses • Family: Orthomyxoviridae • Genus: Influenza virus A • Enveloped virions are 80 to 120 nm in diameter, are 200 to 300 nm long, and may be filamentous – They consist of spike-shaped surface proteins, a partially host- derived lipid-rich envelope, and matrix (M) proteins surrounding a helical segmented nucleocapsid (6 to 8 segments) – The virus envelope glycoproteins (hemagglutinin [HA] and neuraminidase [NA]) are distributed evenly over the virion surface, forming characteristic spike-shaped structures; antigenic variations in these proteins form the basis of the classification system for influenza A virus subtypes – There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) • Human disease historically has been caused by three subtypes of HA (H1, H2, and H3) and two subtypes of NA (N1 and N2) • More recently, human disease has been recognized to be caused by additional HA subtypes, including H5, H7, and H9 (all from avian origin) 9/6/2009 112

Influenza Virus Influenza Type A and Its Subtypes 3 integral membrane proteins that coordinate fusion are : 1. NA Pink - 2. HA Hemagglutinin 3. M2 Yellow - Neuraminidase CDC 9/6/2009 113

Influenza Virus Influenza Type A Influenza A viruses are pleomorphic virions (that is, they vary in shape) They have negative-sense, single-stranded HA - hemagglutinin RNA and an RNA genome that is SEGMENTED There are eight RNA segments in influenza A NA - neuraminidase The nucleocapsid is helical Virions contain RNA polymerase packaged within the virus particle helical nucleocapsid (RNA plus These viruses are enveloped and have two NP protein) membrane glycoproteins: lipid bilayer membrane 1. HA - hemagglutinin - This is the attachment and fusion protein polymerase complex 2. NA - neuraminidase - This is important in release. It removes sialic acid from proteins of the virus and the host cell M1 protein M1 protein underlies the lipid bilayer, is the most abundant protein Genome organized in 7 or 8 segments. 3 integral membrane proteins that coordinate fusion are NA, HA, and M2 (not shown) NP protein important for subtyping NS protein, not shown, important for virulence 9/6/2009 114

ORTHOMYXOVIRIDAE Influenza Type A (H1N1) PROPERTY ORTHOMYXOVIRIDAE Influenza A(H1N1) Genome segmented RNA synthesis nuclear Need for mRNA primer yes Hemagglutinin,neuraminidase Influenza A and B have both but on 2 different proteins (HA and NA) Syncytia formation no (HA functions at acid pH) 9/6/2009 115

Replication of Influenza A Virus • 1. A virion attaches to the host cell membrane via HA and enters the cytoplasm by receptor-mediated endocytosis – HA2 promotes fusion of the virus envelope and the endosome membranes • 2.The major envelope protein M1 dissociates from the nucleocapsid and viral RNA segments are translocated into the nucleus • 3. In the nucleus, the viral polymerase complexes transcribe (STEP 3a) and replicate (STEP 3b) the viral RNA segments • 4. Newly synthesized mRNAs migrate to cytoplasm where they are translated into viral proteins • 5a. Newly synthesised M1 viral proteins move to the nucleus - bind freshly synthesized 21 y y copies of viral RNA segments. • 5 b. Posttranslational processing of HA, NA, and M2 includes transportation via Golgi apparatus to the cell membrane • 6. The newly formed nucleocapsids migrate into the cytoplasm - interact via M1 with a region of the cell membrane where HA, NA and M2 have been inserted • 7. Then the newly synthesized virions bud from infected cell. NA destroys the sialic acid moiety of cellular receptors, thereby releasing the progeny virions 9/6/2009 116

Pandemic (H1N1) 2009 Genetic Origins • HA (or H1): Haemagglutinin type 1 , swine, also in the 1918 influenza Catch host's cell receptors • NA (or N1): Neuraminidase type 1, swine, Eurasian, help start the infection • PA: avian, north America • PB1: human, likely from the 1993 H3N2 influenza • PB2: avian, from north America • NP: swine, north America • M: swine, Eurasia • NS: swine, north America – Non-structural proteins NEP (Nuclear Export Protein):, swine North America 9/6/2009 117

Definition of Pandemic • The word “pandemic” comes from the Greek “pan-“, “all” + “demos”, “people or population” = “pandemos” = “all the people.” • A pandemic affects all (nearly all) of the people. • By contrast, “epi-“ means “upon.” An epidemic is visited upon the people. And “en-“ means “in.” An endemic is in the people. Technical report - Pandemic influenza 9/6/2009 118 preparedness in the EU/EEA

Quadruple Reassortment Result Timeline of 2009 Hybrid “quadruple reassortant” new Pandemic Influenza A(H1N1) 09 Virus —a human No Vaccine virus, an avian virus , and 2 porcine viruses Emergence of Some “Pandemic (H1N1) 2009” Influenza Viruses in H1 Pandemic A(H1N1)v 2009 Virus 3,270 Deaths Avian Humans Influenza Pandemic vaccines 1997: In Hong Kong, avian influenza A (H5N1) H5 Total of 262 Deaths 2009 WHO (Asiatic) Russian H9 1997-2009:avian influenza A (H9N2) Influenza H7 1980- 2003: Avian influenza A (H7N7) B Russian Flu (H2N2) 1889/1890 1 million Russian Flu (H2N2 A/USSR/90/77 (H1N1) 1900 Old Hong Kong Influenza H3N8? Asian 2002 Severer Acute Respiratory Virus (SARS-CoV) 774 deaths Influenza Old Hong Kong Regular vaccines Influenza H2 1957 (Asian Flu) 1-4 million deaths H2N2 Spanish “Triple reassortment” Influenza H3 H2 1968 (Hong Kong Flu) 1-4 million deaths H3N2 Aggressive H3N2 Hong Kong Swine to Human H1 1918 (Spanish Flu) (H1N1) 20-40 million deaths Influenza 1998/9 1918 1957 1968 1977 1993 1997 2003 2009 9/6/2009 By 1993, a bird flu virus had adapted to pigs, grabbed a few human flu 119 US 1976 Swine Influenza virus genes, and infected two young Dutch children, even displaying evidence of limited human-to-human transmission.

Past & Potential Flu Pandemics Summary Epidemics/ Subtype Year Approx Approx Deaths Approx Estimated Epidemics/ Pandemics Infected Mortality % Reproductive Pandemics Number(R0) severity (Asiatic) H2N2 1889/1890 unknown 1 million unknown Unclear Moderate Russian Flu Spanish flu H1N1 1918/1919 500 million 20-50 /?50 million + 2.5 -10% 1.5-1.8 Severe 2nd Wave 3.0-3.5 Asian flu H2N2 1956-58 45 million 1-4 million <0.2% 1.5 Severe Hong Kong flu H3N2 1968-69 50 million 1-4 million >0.2% 1.3-1.6 Moderate Avian flu H5N1 1990-today 438 262 61% 2.14 Severe Ongoing (still researching) SARS SARS-CoV 2002-03 8,096 774 9.6% 0.44-2.29 Severe 1,17 med Swine flu H3N2 1976 250-300 1 0.3% 1.09 Mild Pandemic H1N1 2009 271,253+ 3,280 (ECDC) EST. <0.55% 1.2.-1.8 Moderate (H1N1) 2009 Ongoing CFR- 0.4 Med 1.5 (Mexico) (Fraser 2009) Seasonal Flu A/H3N2, Yearly 1 Billion 250,000-500,000 <0.05% NA NA (Epidemic) A/H1N1, and B 9/6/2009 120

For Any Future pandemic Virus What can and cannot be assumed? • What probably can be assumed: What cannot be assumed: • Modes of transmission (droplet, direct • Antigenic type and phenotype and indirect contact) • Susceptibility/resistance to antivirals • Broad incubation period and serial interval • Age-groups and clinical groups most affected • At what stage a person is infectious • Age-groups with most transmission • Broad clinical presentation and case • Clinical attack rates definition (what influenza looks like) • Pathogenicity (case-fatality rates) • The general effectiveness of personal • ‘Severity’ of the pandemic hygiene measures (frequent hand • Precise parameters needed for modelling and washing, using tissues properly, staying at forecasting (serial interval, Ro) home when you get ill) • Precise clinical case definition • That in temperate zones transmission will • The duration, shape, number and tempo of the waves of infection be lower in the spring and summer than in the autumn and winter • Will new virus dominate over seasonal type A influenza? • Complicating conditions (super-infections) • The effectiveness of interventions and counter-measures including pharmaceuticals • The safety of pharmaceutical interventions ECDC Slides from Evolution of Pandemics 121

20th Century Pandemics • Four pandemics: 1. 1918 Spanish flu – The clinical attack rate in 1918 was estimated to be approximately 25% with 50% of the world’s population becoming infected 2. 1957 Hong Kong flu – In the 1957 pandemic, attack rates of 25-30% were reported 3. 1968 Asian flu – The clinical attack rate in 1968/1969 was 20% were reported 4. 2009: Pandemic (H1N1) 2009 • Each quite different in shape and waves • Some differences in effective reproductive number • Different groups affected • Different levels of severity including case fatality ratio • All pandemics implies different approaches to mitigation ECDC Slides adapted from Evolution of Pandemics 122

Idealised National Curve for Planning, Ireland 2009 Initiation Acceleration Peak Declining 25% Proportion of total cases, consultations, hospitalisations or deaths 20% 15% 10% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 12 Week Single-wave profile showing proportion of new clinical cases, consultations, hospitalisations or deaths by week. Based on London, second wave 1918. ECDC Slides adapted from Evolution of Pandemics Reality is never so smooth and simple 123 Source: Department of Health, UK Animated slide: Please wait

Age-specific Clinical Attack Rate in 60% Previous Pandemics 1957 Kansas City 50% 1957 SE London 1968 Kansas City 1918 New York State 40% 1918 Manchester % with clinical disease 1918 Leicester 1918 Warrington & Wigan 30% 20% 10% 0% 0 20 40 60 80 ECDC Slides adapted from Evolution of Pandemics Age (midpoint of age class) 124 With thanks to Peter Grove, Department of Health, London, UK Animated slide: Press space bar

Numbers affected in seasonal influenza epidemics and pandemics 45% (Overall clinical attack rate in the first wave of previous pandemics) 40% clinical attack rate (%) 35% 30% 25% 20% 15% 10% 5% 0% Seasonal 1918 New 1918 1918 1957 SE 1968 influenza York State Leicester Warrington London Kansas City and Wigan ECDC Slides adapted from Evolution of Pandemics 125

Different Age-specific Deaths in Pandemics 4000 Irelands 1918 deaths per 100,000 by age group: 3500 under 5 years 295 5-10 years 120 3000 10-15 years 103 15-20years 223 2500 20-25 years 329 Deaths 25-35 years 380 2000 35-45 years 239 45-55 years 222 1500 55-65 years 226 65-75 years 221 1000 < 75 years 256 500 Deaths, second wave, 1918 0 epidemic <1 1-2 2-5 5-10 10-15 15-20 20-25 25-35 35-45 45-55 55-65 65-75 75+ Age Group 16000 14000 12000 10000 Deaths 8000 6000 4000 Deaths second wave 1969 2000 pandemic, England and Wales 0 0-4 5-9 10-14 15-19 20-24 25-34 35-44 45-54 55-64 65-74 75+ ECDC Slides adapted from Evolution of Pandemics Age Group 126

1918/1919 Pandemic: A(H1N1) Influenza deaths, England, Wales and Ireland 18,000 16,000 Transmissibility: estimated Basic Reproductive Number (Ro) Deaths in England and Wales 14,000 Ro = 2-3 (US) Mills, Robins, Lipsitch (Nature 2004) Ro = 1.5-2 (UK) Gani et al (EID 2005) Ro = 1.5-1.8 (UK) Hall et al (Epidemiol. Infect. 2006) 12,000 Ro = 1.5-3.7 (Geneva) Chowell et al (Vaccine 2006) 10,000 8,000 6,000 4,000 2,000 0 43 45 47 51 39 41 49 37 27 29 31 33 35 16 18 10 12 14 2 4 6 8 1918 Week #. and Year 1919 1918/19: ‘Influenza deaths’, England and Wales. “The pandemic affected young adults, the very young and older age groups in Ireland” ECDC Slides adapted from Evolution of Pandemics 127

Epidemiology of Ireland Spanish Influenza 1818-1819 Registered Irish deaths per 100,000 by age group during the Spanish Influenza of 1918-1919 400 Number of Registered Deaths 350 300 250 200 380 329 150 295 239 256 100 223 222 226 221 50 120 103 0 Age Groups 9/6/2009 128

Epidemiology of Ireland Spanish Influenza 1818-1819 Summary • Ireland: 10,651 influenza deaths • The deaths per 100,000 by registered age group: – (Unconfirmed approx 11,000 -75,000) under 5 years 295 • Gender – Male : 5,591 5-10 years 120 – Female: 5,060 10-15 years 103 15-20years 223 • Mortality Rate / Region 20-25 years 329 • 243 per 100,000 population 1918 Flu Pandemic In 25-35 years 380 – The mortality rate varied by Ireland 35-45 years 239 region: 45-55 years 222 • Leinster: 304 / 100,000 • Ulster: 302 /100,000 55-65 years 226 • Munster: 159 /100,000 65-75 years 221 • Connaught: 114 /100,000 > 75 years 256 9/6/2009 Credit: Central Statistics Office and PIEG) 129

1968/1969 Pandemic: A(H3N2) Transmitted and Affected all Age Groups 1,400 Seasonal 1,200 influenza GP 'ILI' consultations per week 1,000 800 Initial 600 appearance 400 200 0 20 12 36 44 50 16 24 32 40 48 28 8 12 4 36 20 42 48 28 4 1967 1968 1969 1970 Week no. and year Transmissibility: estimated Basic Reproductive Number (Ro) 1968/69: GP consultations, England and Wales Ro = 1.5-2.2 (World) Cooper et al (PLoS Med.2006) Ro = 2.2 (UK) Gani et al (EID 2005) Ro = 1.3-1.6 (UK) Hall et al (Epidemiol. Infect. 2006) ECDC Slides adapted from Evolution of Pandemics 130

Differing Attack Dates determined by Serology: Serological Attack rate Observed in the UK 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 1969 (first wave) 1970 (second wave) 1957 ECDC Slides adapted from Evolution of Pandemics Courtesy of the Health Protection Agency, UK 131

Idealised Curves for Local Planning 25% Proportion of total cases, consultations, hospitalisations or deaths 20% 15% 10% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Week In reality, larger countries can experience a series of shorter but steeper local epidemics. ECDC Slides adapted from Evolution of Pandemics 132 Animated slide: Press space bar

New UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Local Planning Profiles: Proportion of Local Population Becoming Ill per week 9% UK Planning Proflie Percentage of Local Population 8% Local Planning Profile 7% Less Peaked Local Profile 6% 5% 4% 3% 2% 1% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Week number See Case Study at end of presentation!

Irelands Road to Pandemic Preparedness • 1999 -World Health Organisation (WHO) – “Influenza Pandemic Plan” • 2001- Ireland Developed – “A Model Plan for Influenza Pandemic Preparedness” • 2002- Plan was revised • 2004- Influenza Pandemic Preparedness Plan • 2005- WHO published – “WHO Global Influenza Preparedness Plan” • 2007 - Ireland Developed – “National Plan for Pandemic Influenza” • 2009 – Ireland begins to update National Pandemic Influenza Plan in context to Pandemic Influenza A(H1N1) 09 virus 9/6/2009 134

Scientific Models of the Impact of an Influenza Pandemic • USA: Pandemic Severity Index • United Kingdom: Empiric HPA Model Irelands “National Pandemic Influenza Plan” uses the Empiric HPA Model Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie Gani and Meltzer Model are also used See Website for download for to predict ICU rates and Ro rates in the National Pandemic Plan clinicians 9/6/2009 135

Pre-Pandemic Planning: The Pandemic Severity Index Case Fatality Projected Number of Deaths US Ratio Population 2006 Category 5 >2.0% >1,800,000 1.0 - <2.0% Category 4 900,000 - < 1,800,000 0.5 - <1.0% Category 3 450,000 – < 900,000 0.1% - <0.5% Category 2 90,000 - < 450,000 < 1.0% Category 1 < 90,000 Assumes 30% illness rate and unmitigated pandemic 9/6/2009 without interventions 136

Pandemic Severity Index • Class I • A Class I pandemic is characterized by a widespread novel infection that, while it may cause sickness, does not create large scale deaths or economic impacts. The 1968 Flu is a good example of a Class I pandemic. Also, the current outbreak of Chikungunya could be considered a Class I pandemic. The observed death rate worldwide would not increase significantly from a Class I pandemic. • Class II • A Class II pandemic is characterized by a novel infection that has a low infection rate or a minimal case fatality rate and thus any serious effects on economies or overall mortality rates is minimized. The current HIV/AIDS pandemic can be considered a Class II pandemic. In any one year, a Class II pandemic would kill up to 1 million people. Pandemic (H1N1) 2009 is a Class 2 Pandemic June 12 2009 • Class III • A Class III pandemic is characterized by novel infection that spreads quickly but has a low total mortality rate. The 1918 pandemic would be considered a Class III pandemic. Note: between 50 - 100 million people died during the 1918 pandemic. A class III pandemic would kill approximately 2% of all humans or 120 million people. • Class IV • A Class IV pandemic is characterized by a novel infection that spreads quickly but has a medium level of mortality rates. The Black Death of 1347 - 1350 would be considered a Class IV pandemic. A Class IV pandemic would directly kill 40% of humans. A Class IV pandemic would kill 2.4 billion people. If Influenza A (H1N1) acquires the ability to easily infect humans to humans at the current CFR, it would be a Class IV pandemic. • Class V • A Class V pandemic is characterized by a novel infection that spreads quickly, has a high infection rate and a high mortality rate. There are no documented records of a Class V pandemic, but some experts believe that the new world indigenous peoples were affected by old world diseases in a Class V manner. A class V pandemic would directly kill off approximately 90% of living humans. A class V pandemic would kill 5.4 billion people. 9/6/2009 137

Community Mitigation Strategy by Example on Pandemic Severity Scale 9/6/2009 138

Irelands Pandemic Mitigation “Empiric HPA Model” The Empiric HPA model outlines a single wave pandemic over 15 weeks with a peak of clinical cases and deaths occurring weeks six and seven Proportion of total cases, consultations, Initiation Acceleration Peak Declining 25% hospitalisations or deaths 20% 15% 10% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Proportion 0% 0% 3% 4% 11% 22% 21% 14% 10% 8% 5% 3% 2% 1% 1% Week Number 9/6/2009 139

Irelands Mitigation Strategies • The following scenario has been adopted for planning purposes: • A cumulative clinical attack rate of between 25% and 50% of the population • A hospitalisation rate of between 0.55% and 3.70% • A case fatality rate of between 0.37% and 2.50% (equivalent to the 1957 and 1918 pandemics respectively) • Calculations are based on the Census 2006 Preliminary Report, which puts the Irish population at 4,234,925 9/6/2009 140

Irelands Assumed Clinical Attack Rate: Scenario 1 • Scenario 1 Week % Total cases Cases per week Cases per 100,000 pop Hospitalis ations per Deaths per week • Irish population at week 1 0.1% 1,521 36 8 6 4,234,925 2 0.2% 2,164 51 12 8 Initiation • Considers: 3 4 0.8% 3.1% 8,675 33,041 205 780 48 182 32 122 Acceleration – Clinical Attack Rate of 5 10.6% 111,705 2,638 614 413 25% 1,058,731 cases 6 21.6% 228,189 5,388 1,255 844 Peak – Hospitalisation Rate of 7 21.2% 224,036 5,290 1,232 829 8 14.3% 151,089 3,568 831 559 0.55% 5,823 over the 15 wks 9 9.7% 102,843 2,428 566 381 – Mortality Rate of 10 7.5% 79,863 1,886 439 295 Declining 0.37% 11 5.2% 55,386 1,308 305 205 3,917 deaths 12 2.6% 27,574 651 152 102 13 1.6% 16,580 392 91 61 • Weekly number of cases, 14 0.9% 9,128 216 50 34 15 0.7% 6,939 164 38 26 hospitalisations and Total 100% 1,058,731 25,000 5,823 3,917 deaths as predicted by the empirical model. 9/6/2009 141

Irelands Assumed Clinical Attack Rate: Scenario 2 • Scenario 2 Week % Total cases Cases per week Cases per 100,000 pop Hospitalis ations per week Deaths per week • Irish population at 1 0.1% 3,042 72 113 76 Initiation 2 0.2% 4,327 102 160 108 4,234,925 3 0.8% 17,351 410 642 434 Acceleration 4 3.1% 66,082 1,560 2,445 1,652 5 10.6% 223,410 5,275 8,266 5,585 • Considers : 6 7 21.6% 21.2% 456,377 448,072 10,777 10,580 16,886 16,579 11,409 11,202 Peak – Clinical attack rate of 8 9 14.3% 9.7% 302,178 205,686 7,135 4,857 11,181 7,610 7,554 5,142 50%: 2,117,463 cases 10 11 7.5% 5.2% 159,725 110,772 3,772 2,616 5,910 4,099 3,993 2,769 Declining – Hospitalisation rate of 12 13 2.6% 1.6% 55,147 33,160 1,302 783 2,040 1,227 1,379 829 3.7%: 78,346 over 15 wks 14 15 0.9% 0.7% 18,255 13,879 431 328 675 514 456 347 – Mortality rate of Total 100% 2,117,463 50,000 78,346 52,937 2.5%.: 52,937 deaths 9/6/2009 142

One Possible Irish Pandemic (H1N1) 2009 Scenario Initiation Acceleration Peak Declining 25% Proportion of total cases, consultations, hospitalisations or deaths 20% 15% 10% 5% 0% Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr Month In reality, the initiation phase can be prolonged, especially in the summer months What cannot be determined is when acceleration takes place ECDC Slides adapted from Evolution of Pandemics 143 Animated slide: Press key

WHO Phases 4 and 6 Irelands National Objectives • To assess the extent of human-to-human transmission and determine pandemic risk • To detect, notify and characterise additional clusters (including the identification of risk factors and other data concerning transmission as requested by WHO) • To assess the threat to human health and the impact of any control measures, and identify resources required for enhanced control • To determine and monitor public health resources required for pandemic response • Monitor the global situation (vaccine, antiviral availability, best practice recommendations) and estimate the impact of antiviral programmes (and vaccination programmes if used) 9/6/2009 144

WHO Phase 4-6, Irish Alert Level 1 (Ireland Not Yet Affected) • 1.Establish surveillance of clinical conditions which have been linked to the novel virus abroad, but which are not necessarily part of the clinical criteria for routine influenza investigation • 2.Travellers returning from areas with pandemic activity should be provided with information and advised to seek medical attention if they become unwell. • 3.All doctors should be advised to ask patients presenting with respiratory illnesses about overseas travel • Samples should be collected for influenza detection and sent to the NVRL from all patients with respiratory illness who have: – Fulfilled the case definition for pandemic influenza or been hospitalised with viral pneumonia or – Travelled to areas of known or potential pandemic influenza activity in the week preceding onset of illness or have a flu-like illness and are family members or other close contacts of either of the above • 4.Departments of Public Health must immediately be notified of: – All cases who have been hospitalised with viral pneumonia (or other particular clinical features associated with the pandemic strain that form part of the case definition); and who have travelled to areas of known or potential influenza activity in the week preceding onset of illness and – Those who have a flu-like illness and are family members or other close contacts of a person in either of these categories 9/6/2009 145

WHO Phase 4-6, Irish Alert Level 1 Once Ireland Is Affected! • As soon as the first cases of pandemic influenza are detected in the country the surveillance activities will be focused on: • Detecting community outbreaks • Tracking trends in influenza disease activity and identifying populations that are severely affected • Real-time reporting between he following is essential: – Healthcare institutions – Clinicians – Public Health – Sentinel General Practitioners – NRVL and Laboratories – Pharmacists – 9/6/2009 Etc. 146

Irelands Governmental Lead Agencies, Groups and Committees Emergency/Incident Type Lead Government Lead Principal Support Role Other Potential Support Remarks Department Response Roles Agency as per Framework Influenza Pandemic Influenza and DOHC HSE HSE Local Authorities Pandemic Other Public Health All members of the (DEHLG) Emergencies Interdepartmental CD (DOD) Steering Committee on Revenue Commissioners Public Health Emergency FSAI7 (DHC) Planning Current Pandemic Influenza Emergency Planning Roles and Responsibilities for the Pandemic (H1N1) 2009 9/6/2009 147

Irelands Mitigation Strategies Current Pandemic Roles • “A national plan for pandemic influenza was put in place in January 2007, describing the health system’s response to a possible worldwide pandemic • Additionally The National Pandemic Expert Group has produced Expert Influenza Guidance in November 2008 which is currently being followed. It has met regularly, since an outbreak was first confirmed in Mexico, to assess the public health and clinical guidance to ensure an appropriate level of preparedness and response for Ireland • The Department is in close contact with the World Health Organisation, the European Centre for Disease Prevention and Control and our counterparts in the North of Ireland” Slide Cited From FAQs At DOHC Daily Report 9/6/2009 148

Irelands Mitigation Strategies Current Pandemic Roles • “What is being done currently to prepare for a possible pandemic? • The Department of Health and Children continues to be in close contact with the HSE and the National Pandemic Expert Group • The Department of Health and Children and the HSE participate in regular teleconference meetings with the European Centres for Disease Control, public health officials in other European Member States and the WHO • The Department of Health and Children is the lead government department for public health emergencies and works closely with the HSE in response to pandemic influenza • The National Public Health Emergency Team (NPHET) has been meeting since the outbreak was first confirmed to coordinate the response to this threat – (This is the forum for managing responses between DOHC and the HSE during the planning and response phases of a public health emergency) • NPHET is chaired by the Secretary General of the Department of Health and Children and has been meeting frequently throughout the current situation” Slide Cited From FAQs At DOHC Daily Report 9/6/2009 149

Irelands Mitigation Strategies Current Pandemic Roles • “What is being done currently to prepare for a possible pandemic? • The Government Interdepartmental Committee has been meeting to deal with health emergency planning involving transport, foreign affairs, education, security, etc. • An information leaflet has been printed and distributed to households • Posters and leaflets have been placed in air and sea ports • Ireland have accumulated anti-viral stockpiles to treat half of the population • Anti-viral medication has been distributed through public health departments to treat initial cases as they arise • Advertising will be placed on TV and other media” Slide Cited From FAQs At DOHC Daily Report 9/6/2009 150

Pandemic Influenza A(H1N1) 09 Virus Containment to Mitigation Strategies • Reported aggregated and individual number of cases of influenza A(H1N1)v infection, proportion of individually reported cases, last updates and date of changing to mitigation strategy of EU+3 countries, as of 27 July 2009 9/6/2009 151

Aims of Community Reduction of Influenza Transmission “Mitigation”  Strategy to change from containment to mitigation  Delay and flatten epidemic peak  Reduce peak burden on healthcare system and threat  Reduce total number of cases No intervention Daily cases With interventions ECDC Slides adapted from Evolution of Pandemics Days since first case 152 Based on an original graph developed by the US CDC, Atlanta Animated slide: Press key

World Health Organization (WHO) New Mitigation Strategy for Phase 6 (July, 7,2009 Update) • Strategy to change from containment to mitigation • Public health intervention to clinical intervention • Universal contact tracing to specific contact tracing • Antiviral administration from local DPH to influenza centres GP/pharmacies • New mitigation resources will be available soon from the World Health Organization! – (Thursday, 16, July, 2009) http://www.who.int/mediace ntre/Pandemic_h1n1_presstr anscript_2009_07_07.pdf 9/6/2009 153

Public Health Strategies “Containment” and “Mitigation” Public health strategies against pandemic influenza are characterized in two phases: “Containment” and “Mitigation” “Transition from containment to mitigation phase is necessarily a gradual, phased process. It depends on factors such as epidemic progression (indicated by daily number of new cases and/or the effective reproduction number), disease severity (indicated by proportion of those infected with complications, requiring hospitalisation and case fatality), burden to medical services, resource capacity and effectiveness of containment, and broader considerations in the community Influenza outbreak follows certain progression” • Containment applies when Ireland is free from • Mitigation applies when local transmission of Influenza A(H1N1) 09 virus (Pandemic Phase 5- Influenza A(H1N1) 09 virus (Pandemic phase 6 /Irish alert level 1-2) or when there is 6/Irish Alert level 2-4) becomes significant insignificant local transmission and containment strategy is no longer • Containment (or limiting the entrance and appropriate or feasible initial spread of influenza A (H1N1)v into the • Mitigation (or minimising the impact of the country )involves stringent port health flu virus as its circulation increases) aims at measures, aggressive isolation of cases, contact relieving disease burden and mortality tracing, quarantine and chemoprophylaxis to through hygiene measures, social distancing, cut off disease introduction and transmission medical resource mobilization, self-care and surveillance of acute febrile respiratory illness with or with not pneumonia of a defined high risk group 9/6/2009 154

“Pandemic (H1N1) 2009” “First One Hundred and Seventeen Report” “Chief Medical Officer's Press Conference July, 16, 2009” at www.DOHC.ie Policies and Procedures Overview Transmission Overview • Regionally sporadic cases of mild severity • 8 cases occurred by in-country transmission • “Containment strategies” changed to “mitigation strategies” • 96 cases occurred by out of country transmission for Thursday, July, 16, 2009 • I04 Confirmed Cases • Public Health: • 5 Hospitalization (No Ventilation or deaths) – Clinically contract tracing rather than laboratory tracing • 15 cases under age of 15 years old – Public health invention to general treatment intervention • 4 cases over 65 – No contract tracing • 89 cases between 15 -64 • More females than males • General Practitioners: – Will diagnose and prescribe antivirals by case by case • H1N1 Influenza reporting will be incorporated in normal influenza surveillance via CIDR sentinel physicians • Laboratory : • Shift from viral testing to only testing specific cases • Antivirals : • Will be assessed on severity of case rather than general prophylaxis – No resistance to Tamiflu in Ireland – Tamiflu resistance has occurred in three cases reported China, Japan, Denmark • Vaccines: – Influenza A(H1N1)v vaccine available in August September 2009 – Dissemination of vaccine planning and implementation of the programme is a planning priority – Seasonal vaccine is encouraged for all groups July, 14, 2009 DOHC GP Briefing for “Mitigation” Policy changes! http://www.dohc.ie/issues/swine_i nfluenza/letter_med_pract_140709 .pdf?direct=1 9/6/2009

Irelands Mitigation Strategies Current Pandemic Roles for Pandemic (H1N1) 2009 WHO Phase 6 /Ireland Alert Level 3-4- Treatment Phase “Mitigation” • Containment to Mitigation strategies: • Laboratory : • Shift from viral testing to only testing specific cases “Containment strategies” changed to • Antivirals : “mitigation strategies” as of • Will be assessed on severity of case rather than Thursday, July, 16, 2009 general prophylaxis – No resistance to Tamiflu in Ireland – Tamiflu has occurred in four cases reported China, • Surveillance: Japan, Denmark, Canada – H1N1 Influenza reporting will be incorporated in normal influenza surveillance via CIDR and influenza surveillance reports • Vaccines: – Influenza H1N1 available in August September 2009 • Public Health: – Dissemination of vaccine planning and – Public health invention to general treatment implementation of the programme is a planning intervention priority – Clinically contract tracing rather than laboratory – Seasonal vaccine encouraged for all groups tracing – No contract tracing – Will be updated as more information comes available! • General Practitioners: – Will diagnose and prescribe antivirals by case by case 9/6/2009 156

Irelands Mitigation Strategies Public Health Measures • Public health measures that may be deployed in mitigation phase: • Active promotion and adoption of basic measures: personal protective measures such as hand hygiene and use of face masks; personal care for those who fall ill; environmental hygiene, etc. • Social distancing: school closure, work place contingencies, cancellation of mass gatherings, etc. • Designated clinics operated by Hospital Authority as focused first-line to triage and to look after patients with flu symptoms • Antiviral stockpile mobilized for treatment of patients, chemoprophylaxis of healthcare workers and essential service providers in the public sector • Vaccine administration if available • Mobilize private sector • Private enterprises mobilize business continuity plans • Self-care: Sick patients stay home until their illness is over for at least 48 Hours • Risk communication to different community segments Slide Cited From FAQs At DOHC Daily Report 9/6/2009 157

Dynamic Risk Assessment (DRA) Model Evaluation Form • Incident ID: Pandemic Influenza (2009) • Date: Aug, 30, 2009 Dynamic Risk Assessment (DRA) 0 1 2 3 4 • Completed by: IFPRI Severity Index Score x Confidence Index Score x Spread Index Score x Intervention Index Score x Context Index Score x Latest Analysis Overview: • Score: 13/20 Areas of Improvement are in Blue, others have been met as of Aug 20 2009! • Severity: Remains moderate • Spread: 98-99% are mild cases and 1-2% severe cases worldwide • Interventions: Containment to Mitigation strategies • Context : Measures need to be increased in of public health messages to ascertain ambiguities in mitigation strategies for Flu clinics, antiviral dosages, notification of vaccine tiers and target groups specifically for Pandemic 2009, guidance for pregnancy ,asthmatics, cystic fibrosis , In-country “travellers” ,school resources, summer camps and long term care guidelines ,and national shipping guidelines for specimens, media campaign and a vaccine campaign! General Parameters on following slides

Dynamic Risk Assessment (DRA) Model “Severity Index” • The seriousness of the incident in terms of the intrinsic propensity in a specific circumstance to cause harm to individuals or to a population • Severity and prognosis of known case • The degree of harm already incurred, or likely to incurred by those already affected including, course, complication, death and morbidity rates as obtained from established knowledge, and the spread of onset duration of Illness Grade Qualifier Description Examples Adapted (IFPRI) 0 Very low Seldom causing severe illness Common Cold Swine flu Influenza (SIV) MRSA in a domestic setting 1 Low Occasional severe illness rarely with long term effects or death Hepatitis A in a primary school Seasonal Influenza 2 Moderate Often Severe illness occasionally with long term health effects or death Pandemic Influenza A(H1N) 2009 virus Toxigenic E. coli 0157 Pulmonary TB MRSA infection in high dependency unit Hepatitis B or C Infections Legionnaires Disease Guillain Bar syndrome (GBS) 3 High Usually severe illness often with long term effects or death Meningococcal disease MDRTB HIV/AIDS (most deaths caused by sequelae) 4 Very high Severe illness almost invariably fatal VHF “Ebola” VCJD

Dynamic Risk Assessment (DRA) Model “Spread Index” • The Intrinsic temporal and spatial potential for spread including the infective dose. The virulence of the organism, the availability of the route of spread, the observed spread and susceptibility of the population (eg lack of immunity) in the set of circumstances • Potential of the organism to spread given the circumstance • The transmissibility of the organism, its characteristics (virulence and infective dose) it (s) models of transmission and the availability of the route of infection • The susceptibility of population at risk i.e. the state of immunity, general health and nutrition of the population under consideration and extent to which normal defence mechanisms will protect the population Grade Qualifier Description Examples Adapted (IFPRI) 0 Very low Very low likelihood of spread with very few Single case of Swine flu Influenza (SIV) new cases Single case of campylobacter 1 Low Low likelihood of spread with very few new A single case of meningococcal disease cases Positive case of TB (smear neg) 2 Moderate Moderate likelihood of spread with very few Viral gastro-enteritis in nursing home new cases. A handful of cases of hepatitis occurring May develop into a limited outbreak over a prolonged period of time in a large community Positive smear for TB 3 High High likelihood of spread with many new Endemic/Pandemic Influenza cases. Cholera and dysentery in a deprived May develop into a large outbreak population (children under 8) 4 Very high Spread almost inevitable Measles in a non-immune sub-population

Dynamic Risk Assessment (DRA) Model “Confidence Index” • The level of confidence, epidemiology, clinically, statistically and from laboratory evidence, that the diagnosis is correct in the set of circumstances • Confidence in the hypothesis • Extent of confidence in and consistency of the clinical picture in terms of available laboratory diagnostics results and associated confounding factors including ambiguity and uncertainty Grade Qualifier Description Examples Adapted (IFPRI) 0 Very low Available evidence suggests that a hypothesis Hunch is correct with an empirical probability of less than 10 % 1 Low Available evidence suggests that a hypothesis Alternative hypothesis more likely but is correct with an empirical probability in the cannot exclude the working hypothesis range of 10-25% 2 Moderate Available evidence suggests that a hypothesis Alternative hypothesis equally likely is correct with an empirical probability in the range of 25- 50% 3 High Available evidence suggests that a hypothesis Typical incident picture without conflicting is correct with an empirical probability in the information range of 50-85% 4 Very high Available evidence suggests that a hypothesis Typical incident picture with increasing is correct with an empirical probability higher confirmation than 85%

Dynamic Risk Assessment (DRA) Model “Intervention Index” • The feasibility to intervene to alter the course and influence the outcome of the event in terms of containing, reducing or eliminating the transmission of the organism, or assuaging public anxiety. The feasibility of delivering what is needed to whom is needed, to whom it is needed and when and when and where it is needed, considering the extent to which to interventions are intrinsically simple, effective, available, affordable, cost-effective, acceptable, timely and well targeted Grade Qualifier Description Examples Adapted (IFPRI) 0 Very low Intervention well established with clear benefits and Hand Hygiene (washing advice) no anticipated difficulties to implement Cough and respiratory etiquette advice 1 Low Interventions with clear beneficial effects and few Withdrawal of contaminated food(pork) in a difficulties to implement closed institution Antiviral and vaccinations to a small group of vulnerable contacts A case of influenza in a child with vulnerable contacts to the household 2 Moderate Interventions with some beneficial effects and some Prophylaxis to immediate family and close difficulties to implement contacts in pandemic influenza case where they are dispersed in either low or high risk groups 3 High Some remedial intervention possible but either National food withdrawal difficult to implement, relatively ineffectual or other Urgent mass immunization campaign significant problems Reponses to mass local in-country transmissions to defined high risk groups 4 Very high Remedial intervention very difficult Response to animal and human outbreak of Pandemic influenza( with or without mutation) Acute febrile respiratory illness complicated by pneumonia of high risk group in high dependency unit

Dynamic Risk Assessment (DRA) Model “Context Index” • The broad environment, including public concern and attitudes, expectations, pressures, strengths of professional knowledge and the overall setting of external; factors including politics, in which events are occurring and decisions on responses are being made • 5.1 Media, parents and local concern: – The degree to which media, parents, local concern, politics aggravate and raise the profile of the event under consideration • 5.2 Historical problems: – Influence of local experience of similar interests and previous events, the way they were handled, associated consequences and expectations arising • 5.3 Peer group practice: – Extent to which an established approached or recommended best practice is tested and documented (national guidelines) • 5.4 What is happening elsewhere: – Extent to which other similar incidents are being managed and publicised, with resultant with resultant effect on public attitudes and expectations Grade Qualifier Description Examples Adapted (IFPRI) 0 Very calm No raised level of interest Apathy, Public/media are supportive on immunizations, antivirals treatment, or overall response Common adverse problems are fairly well understood and documented 1 Calm A small degree of increased interest with a low level of conflicting Misunderstanding corrected by routine information factors. Seasonal Influenza immunization campaign Little public concern A few cases of Influenza with local school transmissions 2 Passible Interventions with some beneficial effects and some difficulties to A series of Influenza ,virus transmissions associated with mass implement gathering, schools, residential care homes where acquired infection is low 3 Difficult Context is sensitive with significant difficulties, press interest and local Significant deaths of frontline healthcare workers and people (unaffected)involved. The incident could go very wrong unless children carefully handled. The event could have re-occurred in spite of Widespread in-country transmission affecting several preventative actions schools Unjustified allegations about mitigation measures for school children and pregnancy with media coverage 4 Very difficult Significantly raised public concern and political and emotional pressure Animal and human Pandemic influenza A(H1N1) virus 2009 (with or with the public and the media declaring antagonistic and unhelpful without mutation) linked to new source views Antiviral/pandemic vaccines show to have serious and unexpected side effects for children and pregnancy (eg., Gillian Bar Syndrome GBS)

Pandemic (H1N1) 2009 “The Pandemic!” This preliminary negative stained transmission electron micrograph depicts some of the ultrastructural morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S. Goldsmith and A. Balish. 9/6/2009 164

Influenza Antigenic Changes- Drift • Antigenic Drift • Minor change, same subtype – Caused by point mutations in gene – May result in epidemic • Example of antigenic drift – In 1997, A/Wuhan/359/95 (H3N2) virus was dominant – A/Sydney/5/97 (H3N2) This colorized image, released by the U.S. Centers for Disease Control and appeared in late 1997 and Prevention April 24, 2009, depicts the influenza A H1N1 "swine flu" virus from became the dominant virus an outbreak in 1976 in 1998 9/6/2009 165

Influenza Antigenic Changes - Shift • Antigenic Shift – Major change, new subtype – Caused by exchange of gene segments – May result in pandemic • Example of antigenic shift European Surveillance – H2N2 virus circulated in 1957-1967 Network for Influenza in – H3N2 virus appeared in 1968 and Pigs (ESNIP) completely replaced H2N2 virus 9/6/2009 166

Categorizing Influenza Virus “Viral Nomenclature” Type of nuclear material Neuraminidase Hemagglutinin A/California/04/2009(H1N1)swl Virus Geographic Strain Year of Virus Virus type origin number isolation subtype variant Try These Two! A/Brevig Mission/1/1918(H1N1) 9/6/2009 167 A/New Jersey/76 (Hsw1N1)

Emergence H3N2 Viruses Antigenic Shift 9/6/2009 168

Emergence H3N2 Viruses 9/6/2009 169

Pandemic (H1N1) 2009 Classic Reassortment Diamond 9/6/2009 170

Pandemic (H1N1) 2009 Host Range 9/6/2009 171

Pandemic (H1N1) 2009 Antigenic Shift Pathogenesis • Antigenic Shift – The genetic change that enables a flu strain to jump from one animal species to another, including humans, is called antigenic shift. Antigenic shift can happen in three ways: • Antigenic Shift 1 – A duck or other aquatic bird passes a bird strain of influenza A to an intermediate host such as a chicken or pig. – A person passes a human strain of influenza A to the same chicken or pig. – When the viruses infect the same cell, the genes from the bird strain mix with genes from the human strain to yield a new strain. – The new strain can spread from the intermediate host to humans. • Antigenic Shift 2 – Without undergoing genetic change, a bird strain of influenza A can jump directly from a duck or other aquatic bird to humans. • Antigenic Shift 3 – Without undergoing genetic change, a bird strain of influenza A can jump directly from a duck or other aquatic bird to an intermediate animal host and then to humans. – The new strain may further evolve to spread from person to person. If so, a flu pandemic 9/6/2009 could arise. 172

Genetic Relationships among Human and Swine Influenza Viruses, 1918-2009 • Red arrows indicate human influenza virus lineages, black arrows swine influenza virus lineages, and gray arrows exportation of one or more genes from the avian influenza A virus gene pool. Horizontal bars shown inside the virus represent each of the eight virus genes, abbreviated PB2, PB1, PA, HA, NP, NA, M and NS. Credit: NIAID 9/6/2009 173

Viral Sequencing for Pandemic (H1N1) 2009 • Viral sequencing for BSL3 • A/Kansas/03/2009 (H1N1) Labs: A/Ohio/07/2009 (H1N1) A/California/04/2009(H1N1 A/New York/19/2009 (H1N1) • 1976, the novel A/New A/New York/20/2009 (H1N1) Jersey/76 (Hsw1N1) influenza A/Mexico/4482/2009 (H1N1) • A/California/04/2009 (H1N1) A/Mexico/4486/2009 (H1N1) A/California/06/2009 (H1N1) A/Mexico/4108/2009 (H1N1) A/California/07/2009 (H1N1) A/Mexico/4115/2009 (H1N1) A/California/08/2009 (H1N1) A/Mexico/4603/2009 (H1N1) A/California/10/2009 (H1N1) A/Mexico/4604/2009 (H1N1) A/Texas/04/2009 (H1N1) A/Texas/05/2009 (H1N1) Not an exclusive list 9/6/2009 174

Pandemic (H1N1) 2009 Origins Overview • Nature magazine article on 11 June, 2009, about the “Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic”. 9/6/2009 175

Genetic Components of Triple-Reassortant Swine Influenza A (H1) • Triple-Reassortant Swine Influenza A (H1) Viruses Isolated from 11 Patients between December 2005 and February 2009 in the United States: Triple-Reassortment Swine Tripple-Reassorment Swine H1N1 Influenza Virus H1N2 Influenza Virus (Pts 1-6 and 8-11) (Pt 7 (2007)) Note Pt 7visited a Pig Fair (genetic ressortment H1N2) PB2 PB2 Swine PB1 PB1 Avian PA PA Human HA HA NP NP NA NA M M NS NS http://content.nejm.org/cgi /reprint/NEJMoa0903812.p df (For personal use only) Tripple Reassortment Classical swine, North American Lineage Avian, North American Lineage Human (Seasonal )H3N2 9/6/2009 Human (Seasonal )H1N1 176

Pandemic (H1N1) 2009 “The Pandemic!” Human H1N1 Cases From Human H1N1 Cases From California Triple -Reassortment Swine 1998 Quadruple Reassortment 2009 PB2 PB2 PB1 PB1 PA PA HA HA NP NP NA NA M M NS NS “Quadruple Reassortment” Classical swine, North American Lineage Avian, North American Lineage http://content.nejm.org/cgi/ Seasonal H3N2 reprint/NEJMoa0903812.pdf (For personal use only) Eurasian swine Lineage 9/6/2009 177

H1N1 H3N2 H1N1 (Swine) (Human) (Avian) Pandemic (H1N1) 2009 PB2 PB2 PB2 PB1 PB1 PB1 Virus Lineage Summary PA PA PA HA HA HA NP NP NP Classical swine, North American Lineage NA NA NA Avian, North American Lineage M M M NS NS NS Seasonal H3N2 Eurasian swine Lineage http://www.who.int/csr/resour ces/publications/swineflu/WHO _OFFLU2009_05_15.pdf First Detected in 1998 H3N2 Double Reassortant (Swine/Human) H3N2 Triple Ressortant (Swine/Avian/Human) H1N1 (Swine) ? PB2 PB2 PB2 PB2 PB1 PB1 PB1 PB1 “Large gaps in the historical global animal PA PA PA PA influenza surveillance data. “ HA HA HA HA NP NP NP NP NA NA NA NA M M M M NS NS NS NS Pandemic Influenza A(H1N1) 09 H1N2 Triple Ressortant H1N1 Triple Reassortant Virus Quadruple Reassortant (Swine/Avian/Human) (Swine/Avian/Human) (North American and Eurasian Swine/Avian/Human) PB2 PB2 PB1 PB1 PB2 PA PA PB1 HA HA PA NP NP HA NA NA NP M M NA NS NS M 9/6/2009 NS 178

9/6/2009 179

Phylogenetic Analysis of Sequences of all Genes Identified in A/California/04/2009 • Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team 10.1056/NEJMoa0903810, May 7, 2009 NML Winnipeg, Canada 9/6/2009 180 Has Breakthrough!

Emergence of a Pandemic (H1N1) 2009 Virus in Humans Using “BLAST” Supplement to: Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine origin influenza A (H1N1) virus in humans. N Engl J Med 2009;361. DOI: 10.1056/NEJMoa0903810 (BLAST) Basic Local Alignment Search Tool 9/6/2009 181

“Molecular Clock” Method in Estimation of the Origins of Pandemic (H1N1) 2009 • Britons Andrew Rambaut of the University of Edinburgh and Oliver Pybus of Oxford University, and Yi Guan of the University of Hong Kong examined the genetic sequence of the Pandemic Influenza A(H1N1) 09 Virus The international team used a "molecular clock" method to compare the current virus to its relatives and estimate its age based on the mutations. – This gives a rough idea of when the new virus is likely to have emerged! "We found that the common ancestor of the (new H1N1) outbreak and the closest related swine viruses existed between 9.2 and 17.2 years ago, depending on the genomic segment, hence the ancestors of the epidemic have been circulating undetected for about a decade," 9/6/2009 182

Pandemic (H1N1) 2009 CDC Influenza Laboratory Images • Images below of the newly identified H1N1 influenza virus were taken in the CDC Influenza Laboratory. All Images courtesy of CDC/C. S. Goldsmith and A. Balish. 9/6/2009 183

Pandemic (H1N1) 2009 Laboratory Images • This preliminary negative stained transmission electron micrograph depicts some of the ultrastructural morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S. Goldsmith and A. Balish. • This preliminary negative stained transmission electron micrograph depicts some of the ultrastructural morphology of the A/CA/4/09 swine flu virus. Courtesy of CDC/ C. S. Goldsmith and A. Balish. • Comparison to; • Swine influenza virus. Colorized transmission electron micrograph (37,800X) of the A/New Jersey/76 (Hsw1N1) virus under plate magnification. Image taken during the virus' first developmental passage through a chicken egg. Courtesy of the CDC/Dr. E. Palmer; R.E. Bates. • Negative stained transmission electron micrograph of recreated 1918 influenza virions. Courtesy of CDC/ Dr. Terrence Tumpey E-medicine resource 9/6/2009 184

Pandemic (H1N1) 2009 Epidemiological Risk Factors • Epidemiological risk factors that should raise suspicion of include: • Close contact to a confirmed case of pandemic (H1N1) 2009 virus virus infection while the case was ill • Recent travel to an area where there are confirmed cases of pandemic (H1N1) 2009 virus • Close contact: having cared for, lived with, or had direct contact with respiratory secretions or body fluids of a probable or confirmed case of pandemic (H1N1) 2009 virus 9/6/2009 185

Pandemic (H1N1) 2009 Virus Specific Investigational Triggers • The primary focus of early investigation is to trigger the initial investigation by identifying: • Clusters of cases of unexplained ILI or AFI acute lower respiratory disease • Severe, unexplained respiratory illness occurring in one or more health care worker(s) who provide care for patients with respiratory disease • Changes in the epidemiology of mortality associated with the occurrence of ILI or lower respiratory tract illness, an increase in deaths observed from respiratory illness or an increase in the occurrence of severe respiratory disease in previously healthy adults or adolescents • Persistent changes noted in the treatment response or outcome of severe lower respiratory illness 9/6/2009 186

Pandemic (H1N1) 2009 Infectious Period: • The infectious period for a confirmed case of Pandemic influenza A(H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset or when symptoms cease • The Pandemic (H1N1) 2009 virus in humans is most contagious during the first five days of the illness although some people, most commonly children, can remain contagious for up to ten days ,immunocompromised up to 0-3 months has been documented in seasonal influenza • Remember: if signs and symptoms of influenza persist past this incubation period consider yourself contagious • May 20 2009 : WHO Technical Consultation on the severity of disease Report 20,05 May Teleconferencex • Ranging between – 1–5 days (Spain) – 4–6 days (UK) – 2–7 days (US ) Image courtesy of the CDC/Dr. Erskine L. Palmer; Dr. M. L. Martin. Period of communicability is still unknown ! 9/6/2009 (According to ECDC 3-5 days seems to be prevalent : Aug 21 2009) 187

Pandemic (H1N1) 2009 Virus Transmission: • Direct and indirect contact – Pig to human • asymptomatic carrier pigs – Human to human – Human to Pig – Pig/human to Avian source (turkeys) • Droplet transmission • Aerosol generating procedures (AGPs) • Not transmissible by consumption of pork • Update Aug 18 2009; – WHO/OIE investigating Pandemic (H1N1) 09 turkey isolates in Chile on 2 cordoned turkey farms 9/6/2009 188

Pandemic (H1N1) 2009 Virus Human Signs and Symptoms: Pandemic A(H1N1) 2009 Virus Exacerbation of underlying chronic medical conditions Includes: • Upper respiratory tract disease (sinusitis, otitis media, croup) lower respiratory tract disease (pneumonia, EU ≥38°C bronchiolitis, status *NOTE: Some people, asthmaticus) such as the elderly,  Cardiac (myocarditis, and people who are pericarditis) immunocompromised,  Musculoskeletal (myositis, may not develop a rhabdomyolysis) fever suddenly but  Neurologic (acute and post- gradually infectious encephalopathy, encephalitis, febrile seizures, status epilepticus)  Toxic shock syndrome  Secondary bacterial - Diarrhoea pneumonia with or without sepsis 9/6/2009 189

Pandemic (H1N1) 2009 ECDC Report of Specific Clinical Signs and Symptoms by Systems Update July 17 2009 Frequency of Number of cases % Percentage symptoms (n=879) Generalised Fever or history of fever 653 74% Headache 364 41% Muscle pain 336 38% Joint pain 195 22% Respiratory Dry cough 465 53% Productive cough 157 18% Sore throat 354 40% Runny nose 295 34% Sneezing 165 19% Shortness of breath 103 12% Gastro-intestinal Diarrhoea 101 11% Vomiting 84 10% Nausea 114 13% Other Conjunctivitis 45 5% Nose bleed 25 3% Altered consciousness 12 1% Other (various) 386 44% 9/6/2009 190

High Risk Groups Research in Europe, Ireland and North America Defining the “Pandemic Influenza 2009” High Risk Groups 9/6/2009 191

Pandemic (H1N1) 2009 Travel-related cases

Number of Travel-related Cases by Onset of Disease and Continent of Travel, 20 April to 27 July 2009 (n=2,393)

Pandemic (H1N1) 2009 High Risk Group Age According to ECDC • Distribution by age and travel status of individual case reports of influenza A(H1N1)v infection, 28 EU/EEA countries, as of 13 July 2009 (n=8378) • Distribution by age and travel status of individual case reports of influenza A(H1N1)v infection, 28 EU/EEA countries, as of 13 July 2009 (n=8400) 9/6/2009 194

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Distribution of travel-related and domestic individual case reports of influenza A(H1N1)v infection, by date of onset and area of travel, 28 EU/EEA countries, 11 April – 13 July 2009 (n=5768) 9/6/2009 195

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Distribution by age and gender of individual case reports of influenza A(H1N1)v infection, 28 EU/EEA countries, as of 13 July (n=7406) • Distribution by age and gender of individual case reports of influenza A(H1N1)v infection, 28 EU/EEA countries, as of 13 July 2009 (n=7406) 9/6/2009 196

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Reported number of cases of influenza A(H1N1)v infection, association with travel, and hospital admission, 29 EU/EEA countries, as of 7 August 2009 http://www.ecdc.europa.eu/en/files/pdf/Health_topics/ 9/6/2009 090810_Influenza_A(H1N1)_Analysis_of_individual_data _EU_EEA-EFTA.pdf 197

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Distribution of number of confirmed cases of A(H1N1)v infection by week of onset (n=6 994) and notification rate (per 100 000) by reporting week (n=26 163), 28 EU/EEA countries, as of 7 August 2009 9/6/2009 198

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Proportion of hospitalised cases of influenza A(H1N1)v among the total number of cases reported in 27 EU/EEA countries, by week of onset 20 April – 26 July 2009 (n=6 567) 9/6/2009 199

Pandemic (H1N1) 2009 According to ECDC Surveillance Report • Age distribution among hospitalised and non-hospitalised cases, among A(H1N1)v cases reported in 27 EU/EEA countries (n=8 974) • Age distribution in countries with low (n=2 629) and high hospitalisation rates (n=1 118) 9/6/2009 200

Pandemic (H1N1) 2009 Predefined Underlying conditions According to ECDC • Probability of being in hospital according to characteristics of A(H1N1)v cases reported in 25 EU/EEA countries (n=3 805) 9/6/2009 201

ECDC Summary • “Individual data were reported on 9,750 confirmed cases of influenza A(H1N1)v infection by 28 EU/EEA countries up to 7 August 2009 (62 % reported by the United Kingdom) – The mean notification rate in 26 EU/EEA countries was estimated to 5.3 per 100 000 population (ranging from 0.2 to 19.5) over a period of three months (May–July) – There is an association between receiving treatment and hospitalisation, RR=1.29 (1.15–1.26) – The proportion of hospitalised cases is higher among patients who have developed complications than among patients reported without any complication, RR=5.67(3.45–9.32) – In countries with a low proportion of hospitalisation, patients with underlying conditions are more likely to be hospitalised. RR=1.5 (1.07–2.17)” 9/6/2009 202

Regional Pandemic (H1N1) 2009 Activity by HSE-Area Week 30 • Map of influenza activity by HSE area as of July, 26, 2009 (n=217) HSE-North West - 6 HSE-NE- 26 HSE-Midlands - 8 HSE-West- 21 HSE-Midlands West- 17 HSE-South- 19 HSE-South East- 18 HSE-East - 102

HSE Areas of Confirmed Cases Of Pandemic (H1N1) 2009 Virus • Summary of all HSE reported confirmed cases of influenza A(H1N1)v 09 – Number and rate per 100,000 population for confirmed cases by all HSE areas As of July, 26, 2009 # of Pandemic Influenza Rate/100,000 population (n=217) A(H1N1)v Confirmed Cases HSE-East 102 6.8 HSE-Midlands 8 3.2 HSE-Midlands West 17 4,7 HSE-North East 26 6.6 HSE-North West 6 2.5 HSE-South East 18 3.9 HSE-South 19 3.1 HSE-West 21 5.1 Total 217 5.1

Pandemic Influenza A(H1N1)v Transmission Modes • Number of confirmed cases of influenza A(H1N1)v by mode of transmission and week of notification (n=217) – 64 percent (n=139) were travel related (imported) – 8% (n=17) were contacts of an imported case (secondary import related) – 2% (n=4) were linked to a non‐imported case (tertiary indigenous) – 5% (n=11) had no history of travel and no known links to other confirmed cases (sporadic indigenous)

Pandemic Influenza A(H1N1)v 09 Confirmed Cases By Gender and Age • Number of confirmed cases of influenza A(H1N1)v and notification rate per 100,000 population by age group (n=217) – 110 were female (50.7%) – 107 were male (49.3%) – The median age of cases was 23 years (range: 0‐73 years) – 66% of cases were less than 30 years of age

CIDR-2 Notifications of Influenza • Shows the number of CIDR notifications of influenza by type and week of notification compared to sentinel GP ILI consultation rates per 100,000 population during the 2008/2009 and the summer 2009 influenza seasons. 9/6/2009 207

Pandemic (H1N1) 2009 Outbreak In Ireland By Age, Gender and Transmission Mode Update as of July ,18 ,2009 from Weekly Surveillance Report Age Male Female Total Antiviral In-Country Out-of-Country Unknown Hospitalizations Treatment Transmission Transmission Transmission <1yrs 3 1 4 -- - - - - 1-4 7 5 12 9 - - - - 5-9 3 3 6 4 - - - - 10-14 2 3 5 5 - - - - 15-19 10 11 21 11 - - - - 20-24 15 13 28 23 - - - - 25-34 12 21 33 17 - - - - 35-44 12 8 20 9 - - - - 45-54 4 7 11 4 - - - - 55-64 6 4 10 5 - - - - 65+ 2 3 5 5 - - - - School Outbreak - - - 28+ - - - - Total 76 79 155 117+ 16 (Unknown age) 123 (unknown age) 16 12 (Unknown age) 9/6/2009 208

Early Epidemiology of Pandemic (H1N1) 2009 In Ireland (n-29) • In Ireland, 29 confirmed cases of influenza A (H1N1) infection have been reported since week 18 2009 • Age and Sex Of the 29 cases reported to date, 17 are female (58.6%) and 12 are male (41.4%) • The female to male sex ratio is 1.4:1.0 • The median age of cases is 27.0 years (range: 1-73 years). • The mean age is 27.7 years 9/6/2009 July, 7, 2009 Article 209

Early Epidemiology of Pandemic (H1N1) 2009 In Ireland (n-29) • Younger age groups appear to be at greatest of illness. Among those affected to date, only one case, aged greater than 65 years was noted to have underlying co-morbidities. This patient was hospitalised due to a secondary chest infection. Underlying chronic disease have been reported in two (6.9%) cases. These include: type 1 diabetes mellitus, chronic obstructive pulmonary disease, heart disease and chronic liver disease. Figure 3 shows the number of confirmed influenza A(H1N1) cases by symptom. 9/6/2009 July, 7, 2009 Article 210

Pandemic (H1N1) 2009 United Kingdom Weekly Surveillance Report • As of July 23 2009 • GP consultation rates have risen sharply over the last week in England. • HPA estimates that there were 100,000 new cases of swine flu in England last week (range 60,000 - 140,000 • The under-5s and 5-14 year olds are the age groups predominantly affected, with the over 65s continuing to show much lower rates • The majority of cases continue to be mild 9/6/2009 211

Case study of High Risk Groups In Canada • Laboratory-confirmed Canadian Pandemic (H1N1) 2009 cases, hospitalized cases, cases admitted to ICU and deaths with core information available, reported to the Public Health Agency of Canada as of 25 July 2009 • Highest hospitalization rate is among High Risk Age Groups Mortality rate the cases below 1 year of age (25.1 per 100,000) followed by the cases <1 year 0.27 per 100,000 between 1 and 4 years of age (10.0 >65 0.33 per 100,000 per 100,000). • Pregnant women within the severe cases (21.9% for hospitalized cases and 33.3% among deaths) 9/6/2009 213

Case study of High Risk Age Groups In USA A. Novel H1N1 Confirmed and Probable Case Rate in the United States, By Age Group B. Novel H1N1 U.S. Hospitalization Rate per 100,000 Population, By Age Group C. Novel H1N1 U.S. Deaths, By Age Group 9/6/2009 214

Pandemic (H1N1) 2009 Mexico, United Sates, Canada Age Early Report Summary: In Mexico In United States: As of 20 May 2009, 16:30 AM ET, 48 states of the United States have reported a total of 5,764confirmed cases including 247 hospitalizations and 8 deaths. Median age: 17 years, range 1 month- 87 years Gender: 51% female, 49% male Underlying medical conditions (n=44): 63% (median age: 18 years) Median time from illness onset to hospital admission (n=32): 4 days (range: 1-13 days) Median length of hospital stay (n=32): 5 days (range 2-31) In Canada: As of May 28, 2009, the average age reported is 22 years or younger (median: 17 years; range: <1 – 86 years). In Europe: Median age 33 9/6/2009 215

Pandemic (H1N1) 2009 High Risk Groups: • There is sufficient data available at this point to determine who is at higher risk for complications of Pandemic (H1N1) 2009 virus infection • Considered higher risk for pandemic (H1N1) 09 virus Five-year-old Edgar Hernandez, known as "patient zero" survived complications if: the earliest documented case of swine flu. “April 2 2009” 9/6/2009 216

Groups at High Risk for Complications From Pandemic (H1N1) 2009 Virus Summary • High Risk groups include: • Chronic liver disease – Cirrhosis • Age – Chronic hepatitis – Persons aged 65 years or older – Inflammatory bowel disease – Infants aged 12–24 months; Children <5 (children <2 • Chronic metabolic disorders are at particular risk of influenza) – Addison’s disease • Pregnancy – Diabetes mellitus requiring insulin or oral – Especially during third trimester and four weeks post- hypoglycaemic drugs partum – Phenylketonuria • Bariatric – Sickle cell anaemia and other haemoglobinopathies – BMI ≥40 • Immunosuppression and malignancy due to • Chronic respiratory disease disease or treatment – Asthma requiring continuous or repeated use of – Asplenia or splenic dysfunction inhaled or systemic steroids or with previous – HIV infection at all stages exacerbations requiring hospital admission – Malignancy – Children who have previously been admitted to hospital with lower respiratory tract disease – Patients undergoing chemotherapy or transplant leading to immunosuppression – Such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults – Individuals on or likely to be on systemic steroids for more than a month at a dose equivalent to • Chronic heart disease prednisolone at 20mg or more per day (any age) or for – Hemodynamically significant cardiac disease children under 20kg a dose of 1mg per kg per day – Congenital cardiac disease – Diseases that requiring long-term aspirin therapy – Hypertension with cardiac complications rheumatoid arthritis or Kawasaki disease – Chronic heart failure • Chronic neurological disease – Individuals requiring regular medication and/or follow – Neuromuscular disorders up for ischaemic heart disease – Seizure disorders • Chronic renal disease – Cognitive dysfunction that may compromise the handling of respiratory secretions Not an inclusive list! 217 9/6/2009

HPSC High Risk Groups Personal Resources • As of 18th Aug 2009: People with specific medical /CF/HIV conditions update Page 1-10 Page 1-11 Page 1-8 http://www.hpsc.ie/hpsc/A- http://www.hpsc.ie/hpsc/A- http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemic Z/EmergencyPlanning/AvianPandemicI Z/EmergencyPlanning/AvianPandemicI Influenza/SwineInfluenza/Adviceforth nfluenza/SwineInfluenza/Adviceforthe nfluenza/SwineInfluenza/Adviceforthe eGeneralPublic/File,3922,en.pdf GeneralPublic/File,3731,en.pdf GeneralPublic/File,3733,en.pdf 9/6/2009 218

Pandemic (H1N1) 2009 Virus HPSC On Personal Resources • New update as of 4th September 2009” “Information about Pandemic (H1N1) 2009 (Pandemic influenza) for women who are pregnant or are breastfeeding” http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluen za/AdvicefortheGeneralPublic/File,3732,en.pdf 9/6/2009 219

Pandemic (H1N1) 2009 General Diagnosis • A Confirmed case of Pandemic Influenza A(H1N1) 09 Virus infection is defined as an individual with laboratory confirmed Pandemic (H1N1) 2009 virus infection by one or more of the following tests: • Real‐time RT‐PCR ICycler® from • Viral culture BioRad • Four‐fold rise in Pandemic Influenza A(H1N1) 09 Virus specific neutralizing antibodies 9/6/2009 220

WHO Case Definitions to be Used For Investigations of Pandemic (H1N1) 2009 Virus Cases • Clinical case description • Acute febrile respiratory illness (fever ≥38°C) with the spectrum of disease from influenza‐like illness to pneumonia. • 1. A Confirmed case of swine influenza A(H1N1) virus infection is defined as an individual with laboratory confirmed swine influenza A(H1N1) virus infection by one or more of the following tests*: – real‐time RT‐PCR – viral culture – four‐fold rise in swine influenza A(H1N1) virus specific neutralizing antibodies. • 2. A Probable case of swine influenza A(H1N1) virus infection is defined as an individual with an influenza test that is positive for influenza A, but is unsubtypable by reagents used to detect seasonal influenza virus infection OR • A individual with a clinically compatible illness or who died of an unexplained acute respiratory illness who is considered to be epidemiologically linked to a probable or confirmed case. 9/6/2009 221

EU Case Definition Pandemic (H1N1) 2009 Virus April,30,2009 • Clinical criteria • At least one of the following three in the • Any person with one of the following seven days before disease onset: three: • — a person who was a close contact to a confirmed case • — fever ≥38°C AND signs and symptoms of novel influenza A(H1N1) virus infection while the case of acute respiratory infection, was ill, • — pneumonia (severe respiratory illness), • — a person who has travelled to an area where sustained human-to-human transmission of novel • — death from an unexplained acute influenza A(H1N1) is documented, respiratory illness. • — a person working in a laboratory where samples of • Laboratory criteria the novel influenza A(H1N1) virus are tested. • At least one of the following tests: • — RT-PCR, • Case classification • — viral culture (requiring BSL 3 facilities), • A. Case under investigation Any person meeting the • — four-fold rise in novel influenza virus clinical and epidemiological criteria. A(H1N1) specific neutralising antibodies (implies the need for paired sera, from • B. Probable case acute phase illness and then at • Any person meeting the clinical AND epidemiological convalescent stage 10-14 days later criteria AND with a laboratory result showing positive minimum). influenza A infection of an unsubtypable type. • Epidemiological criteria • C. Confirmed case • Any person meeting the laboratory criteria for confirmation. 9/6/2009 222

NDSC Case Definition Influenza (Influenza A and B virus) (EU) • Clinical description • Clinical picture compatible with influenza i.e. sudden onset of disease, cough, fever ≥38°C, muscular pain and/or headache. • Laboratory criteria for diagnosis • One of the following: – Detection of influenza antigen, or influenza virus specific RNA – Isolation of influenza virus – Demonstration of a specific serum antibody response to influenza A or B (four fold or greater rise).** • Case classification • Possible: Clinically compatible case with epidemiological link* • Probable: N/A Case Definitions for Notifiable Diseases Infectious Diseases (Amendment) • Confirmed: Clinical case that is laboratory confirmed. (No. 3) Regulations 2003 (SI No. 707 of 2003) • Note: Influenza of a new or re-emergent subtype is defined as influenza caused by a novel or re-emerging influenza virus which is capable of infecting humans and causing human illness, and to which a large 9/6/2009 223 proportion of the human population has little or no immunity.

Reporting Suspect Pandemic (H1N1) 2009 Virus Infection • Clinicians must contact their national lead agency /public health department to report suspected cases of Pandemic Influenza A(H1N1) 09 Virus infection and to obtain information on what clinical and epidemiological data to collect and specimen shipment protocols in their region. 1.Health and Safety regulations on biological hazards (Safety, Health and Welfare at Work Act 2005 (No. 10 of 2005) 2.European Agreement concerning the International Carriage of Dangerous Goods by road (ADR) Regulations (2007 edition). 3.S.I. No 29 of 2004 - Carriage of Dangerous Goods by Road Regulations, 2004. 9/6/2009 224

Influenza Activity Index Irish Influenza Activity Code, Name and Description Update 20th Aug 2009 Index Index Name Index Description* Code 0 No Report No reports received. 1 No Activity “No ILI or laboratory confirmed influenza cases and no influenza/ILI outbreaks in a HSE-Health Area.” No Influenza-like illness AND No NVRL laboratory confirmed influenza cases AND No influenza/ILI outbreaks. 2 Sporadic Activity “Isolated case(s) of ILI or laboratory confirmed influenza case(s) in a HSE-Health Area, or an influenza/ILI outbreak in a single institution.” Isolated case(s) of ILI OR Isolated NVRL laboratory confirmed influenza case(s) OR 1 influenza/ILI outbreak in a single institution. 3 Localised Activity “Increases in ILI in local areas (such as a city, county, or district) within a HSE-Health Area, or outbreaks in two or more institutions within an area, with laboratory confirmed cases of influenza infection. Levels of activity in the remainder of the HSE-Health Area would be sporadic or have no activity” NVRL laboratory confirmed cases of influenza infection. AND Outbreaks in ≥2 institutions in same HSE-Area OR Increases in ILI in local areas (such as a city, county, or district) within a HSE- Area Levels of activity in the remainder of the HSE- Area would be sporadic or have no activity. 4 Regional Activity “Increases in ILI in one or more regions with a population comprising less than 50% of the HSE-Health Area’s total population, with laboratory confirmed influenza cases in the affected region(s). Levels of activity in the remainder of the HSE-Health Area would be sporadic or have no activity.” NVRL laboratory confirmed influenza cases in the affected region(s). AND Increases in ILI in ≥1 regions with a population comprising less than 50% of the HSE- Area’s total population, Levels of activity in the remainder of the HSE- Area would be sporadic or have no activity. 5 Widespread activity “Increases in ILI in one or more regions with a population comprising 50% or more of the HSE-Health Area’s total population, with laboratory confirmed influenza infections” (N-13) Increases in ILI in≥1 regions with a population comprising 50% or more of the HSE- Area’s total population, AND NVRL laboratory confirmed influenza infections. 9/6/2009 225

Influenza-like illness (ILI) –Definition Community Surveillance of Clusters/Outbreaks • Influenza-like illness (ILI) -definition for interim surveillance of clusters/outbreaks • Three or more cases of ILI arising within the same 72 hour period which meet the same clinical case definition and where an epidemiological link can be established • ILI symptoms include: – Acute onset of fever (temperature ≥38°C) – OR history of fever – AND flu-like illness (two or more of the following symptoms: cough, sore throat, myalgia, headache, rhinorrhea or vomiting/diarrhoea) Influenza-like Illness/Influenza/Influenza A (H1N1) Outbreak Reporting Form ILI GP consultation rates per 100,000 population, baseline ILI threshold rate and number of positive influenza specimens detected by the NVRL by influenza week and season 9/6/2009 226

Algorithm for the Primary Care Management • As of July, 29, 2009 the Interim algorithm for the PRIMARY CARE Management of Persons who may have Influenza A(H1N1)v will be used during WHO phase 6 – Irish alert level 2-3 of Irelands mitigation strategy ! Letter From Dr Kevin Kelleher National Director Health Protection July, 29, 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/Swine Influenza/AdviceforHealthProfessionals/GPs/File,3892 ,en.pdf 9/6/2009 227

DOHC FAQs for Antiviral Treatment • July 16 2009 • Who will receive anti-viral treatment and where is it available? – Patients who appear to have severe symptoms – Patients who are in defined high risk groups – All suspected cases who have a household contact in a very high risk group • Who are those considered to be in a high risk group and needing treatment? • People who have: chronic lung, heart, kidney, liver, or neurological disease; people whose immune system is reduced by disease or medications; people with diabetes mellitus; people aged 65 years and older; children under 5 (children under 2 are at particular risk of influenza); people on medication for asthma, severely obese people (body mass index more than 40) and pregnant women. • Who are the contacts of cases who will require treatment even though they do not have the illness? – Pregnant women http://www.nutritionandheal th.ie/Sectors/NHF/NHF.nsf/v – Those on treatment for asthma Pages/Keeping_Fit~bmi- – Those who are very obese (Body Mass Index >40) calculator?OpenDocument BMI calculator http://www.dohc.ie/issues/swine_influenza/faqs.pdf?direct=1 9/6/2009 228

Public Health Management of Pandemic (H1N1) 2009 Virus (Mitigation Phase) • Public Health: – Mandatory reporting to DPH/MOH of influenza-like illnesses and acute febrile respiratory illnesses – Clinically contact tracing rather than laboratory tracing – Public health intervention to general treatment intervention – No contact tracing – Contact tracing for the defined high risk groups with routine GP homecare referrals and follow up by Public Passive Screening Poster Health Nurse placed in hospital ! – Promotion of Influenza education on vaccinations, hygiene etc – Encourage assessment, planning, implementation and evaluation of Influenza Care Centres (ICC) within the Republic of Ireland for upcoming vaccination season to decrease surge capacity at hospitals and GP offices 9/6/2009 229

Pandemic (H1N1) 2009 Mitigation Case Surveillance Form • Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie • See Website for download for clinicians http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/Advice forHealthProfessionals/PublicHealth/Surveillance/File,3606,en.pdf Aug,11, 2009 1-3 pages 9/6/2009 230

Pandemic (H1N1) 2009 Dispatchers Guide Infection Prevention and Control Guidance for the Emergency Dispatcher • Recommendations for 999 • It is important for the Emergency Operators to question callers to ascertain if there is anyone at the incident location who is possibly afflicted by the Pandemic (H1N1) 2009,to communicate the possible risk to EMS personnel prior to arrival, and to assign the appropriate EMS resources • Emergency Operators should review existing medical dispatch procedures and coordinate any modifications with their EMS medical director and in coordination with their local department http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/Avian of public health PandemicInfluenza/SwineInfl uenza/AdviceforHealthProfes sionals/AmbulanceStaff/File, 9/6/2009 3601,en.pdf 231

Pandemic (H1N1) 2009 Dispatchers Guide Infection Prevention and Control Guidance for the Emergency Dispatchers Interim recommendations: • Call takers should screen all callers for any symptoms of acute febrile respiratory illness. – Callers should be asked if they, or someone at the incident location, has had nasal congestion, cough, fever or other flu-like symptoms – If the emergency operator call taker suspects a caller is noting symptoms of acute febrile respiratory febrile illness, they should make sure any first responders and EMS personnel are aware of the potential for “acute febrile respiratory illness” before the responders arrive on scene 9/6/2009 232 Adapted from “Dispatchers Guide to CBRNE”

Confirmed Pandemic (H1N1) 2009 Virus in The Geographic Area • Step 1: Address scene safety: – If emergency operator advises potential for acute febrile respiratory illness symptoms on scene, EMS personnel should don PPE for suspected cases of swine-origin influenza prior to entering scene. – If emergency operator has not identified individuals with symptoms of acute febrile respiratory illness on scene, EMS personnel should stay more than 6 feet away from patient and bystanders with symptoms and exercise appropriate routine respiratory droplet precautions while assessing all patients for suspected cases of swine-origin influenza. • Step 2: • Assess all patients for symptoms of acute febrile respiratory illness (fever plus one or more of the following: nasal congestion/ rhinorrhea, sore throat, or cough). – If no symptoms of acute febrile respiratory illness, provide routine EMS care. – If symptoms of acute febrile respiratory illness, don appropriate PPE for suspected case of swine-origin influenza if not already on. 9/6/2009 233

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Guidance for the Ambulance Service • If the ambulance service is informed that a patient is suspected or confirmed to have Pandemic Influenza A(H1N1) 09 Virus the following precautions should be taken: • 1.On arrival to the house/healthcare facility – Ambulance staff to decontaminate hands (alcohol gel) – Routine care (Infection control precautions for caring for a patient with suspected or confirmed influenza A (H1N1)v) – Wear surgical mask, plastic apron/gown, gloves (& goggles if splash/spray risk) – Aerosol generating procedures (refer to Aerosol Generating Procedure Document) – FFP2 or FFP3 mask (fit check to ensure a good seal), goggles, long sleeved disposable gown and gloves • Inform the hospital of admission of potentially infectious person Before leaving the house/healthcare facility • Request patient to wear a surgical mask and advise of respiratory An ambulance driver hygiene and cough etiquette wearing a face mask – (education leaflet if possible) drives in Hospital La Fe in • A patient with suspected or confirmed flu should not travel with any Valencia, Spain other patients 9/6/2009 234

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Guidance for the Ambulance Service In ambulance: • Change gloves and decontaminate hands after every patient procedure • Use single use or single patient use medical equipment where possible • Use disposal linen if available http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPande micInfluenza/SwineInfluenza/Advic eforHealthProfessionals/Ambulanc eStaff/File,3627,en.pdf 9/6/2009 235

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Guidance for the Ambulance Service • Arrival to hospital • Ensure arrangements in place for receipt of the patient before the patient leaves the ambulance • Transfer patient to the care of hospital staff • Remove PPE in the following order 1. Gloves (avoid touching the outside of the gloves) 2. Decontaminate hands 3. Eye wear (if applicable) 4. Mask Remove mask by breaking the ties. 5. If ties are elastic grasp and lift ties from behind your head and pull off mask away from your face . Avoid touching the front of the mask & use ties to discard 6. Discard all PPE into healthcare risk waste 7. Decontaminate hands 9/6/2009 236

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Guidance for the Ambulance Service • Before ambulance is used again • Cleaning and disinfecting(wear appropriate PPE while cleaning) – Surfaces (stretcher, chair, door handles etc) should be cleaned with a detergent and a hypochlorite solution 1000pmm • Laundry – Place reusable blankets in an alginate bag, then into a red laundry bag and sent for laundry • Medical equipment – Follow manufacturer’s instructions for cleaning/disinfecting reusable equipment • Management of waste – All masks and any waste contaminated with blood or body fluid (including respiratory secretions) should be disposed of as Healthcare Risk waste – Management of sharps – as per Standard Precautions – Management of blood and body fuids – as per Standard Precautions 9/6/2009 237

Pandemic (H1N1) 2009 Who's Summary of Clinical Guidelines Modalities Strategies Antibiotics In case of pneumonia, empiric treatment for community acquired pneumonia (CAP) per published guidelines pending microbiologic results (e.g. 2-3 days); tailored therapy thereafter if pathogen(s) identified. Antiviral therapy If treatment needed, oseltamivir or zanamivir. The new influenza A (H1N1) virus is currently resistant to amantadine and rimantadine. Corticosteroids Moderate to high dose steroids are NOT recommended. They are of unproven benefit and potentially harmful. Infection control Standard plus Droplet Precautions. For aerosol-generating procedures use particular respirator (N95, FFP2 or equivalent), eye protection, gowns, gloves, and an airborne precaution room, that can be naturally or mechanically ventilated, per WHO guidance NSAIDS, Paracetamol or acetaminophen given orally or by suppository. Avoid antipyretics administration of salicylates (aspirin and aspirin containing products) in children and young adults (< 18 years old) due to risk of Reye’s syndrome. Oxygen therapy Monitor oxygen saturation and maintain SaO2 over 90% (95% for pregnant women) with nasal cannulae or face mask. 9/6/2009 238

Pandemic (H1N1) 2009 Virus Triage Health Care Setting Guidelines Resource 9/6/2009 239

HPSC Adaptation from WHO- “Patient Care Checklist” Pandemic (H1N1) 2009 20th Aug 2009 20th Aug 2009 Update June 2009 July, 16, 2009 HPSC is being proactive and showing continuous improvement through July, 29, 2009 innovation in all guidance 9/6/2009 documents! 240

Pandemic (H1N1) 2009 Virus Advice to General Practitioners on Management of a Possible Case Resources • Update July, 16, 2009 • Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie • See Website for download for clinicians or hit hyperlink during slide show! http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflu enza/SwineInfluenza/AdviceforHealthProfe ssionals/GPs/File,3636,en.pdf 9/6/2009 241

Pandemic (H1N1) 2009 General Practitioners Algorithm and Infection Control Resources Update July, 29, 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInf luenza/SwineInfluenza/AdviceforHealthP rofessionals/GPs/File,3636,en.pdf 9/6/2009 242

Pandemic (H1N1) 2009 Advice to General Practitioners on Management in context to “Mitigation” July, 14,2009 Letter from DOHC/HSE July, 29,2009 Letter from HSE HPSC Summary of both Letters http://www.dohc.ie/issues/swine_influenza/lette r_med_pract_140709.pdf?direct=1 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/S wineInfluenza/AdviceforHealthProfessionals/GPs/ File,3869,en.pdf http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/Swine Influenza/AdviceforHealthProfessionals/AntiviralMedi cines/File,3857,en.pdf 9/6/2009 243

Interim Algorithm for the Emergency Department Management of Adults Who May Have Influenza A(H1N1)v Update as of August, 4, 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemi cInfluenza/SwineInfluenza/Advicefor HealthProfessionals/HospitalClinician s/File,3894,en.pdf

Interim Algorithm for the Emergency Department Management of Children Who May Have Influenza A(H1N1)v Update as of August, 4, 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflu enza/SwineInfluenza/AdviceforHealthProfe ssionals/HospitalClinicians/File,3895,en.pdf

Pandemic (H1N1) 2009 Triage Tents • Influenza Triage Tent • East Palo Alto, CA • Interior – Influenza Triage Tent outside emergency department 9/6/2009 246

Pandemic (H1N1) 2009 Triage Initial GP Patient Management • Should be managed as follows: • Physical barrier (i.e. window or plexiglass barrier) or the receptionist should maintain a 2 metre (6 foot) distance from all patients whenever possible • In settings where such a separation is not possible, healthcare workers are advised to maintain whatever separation is feasible • If there is no barrier, and a 2 metre (6 foot) distance cannot be achieved, a fit tested FFP 2-3 respirator and eye protection should be worn by the receptionist • Alcohol-based hand rub (ABHR) should be readily available for both staff and patients • Patient should be asked to perform hand hygiene using an ABHR and given a surgical mask to put on covering their nose and mouth • Patient should be placed in a separate area of the office (i.e. examination room). If an examination room or separate room is not available, the patient should remain masked • Provide hands-free garbage and laundry receptacles • Remove magazines and toys from the waiting rooms to reduce potential contact exposures 9/6/2009 247

Pandemic (H1N1) 2009 Triage Health Care Setting Screening • All patients who present to a health care setting should be screened for fever and respiratory symptoms. • This should include: • Passive screening: visual alerts posted at the entrances to all health care settings asking patients to report whether they have fever and any new or worsening respiratory symptoms, and • Active screening: At first contact, staff asks about fever and respiratory symptoms • Respiratory symptoms include cough, sore throat, coryza (runny nose), and myalgias (general body aches) • Standard, contact and droplet precautions for clinicians • Additional precautions Influenza-like Illness/Influenza/Influenza A (H1N1) Outbreak Reporting Form 9/6/2009 248

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • The following infection control practices are indicated when assessing patients with fever and respiratory symptoms: • Before a clinical assessment: • Ensure patient is still wearing a surgical mask • Perform hand hygiene (alcohol based hand rub or soap and water) before and after patient assessment • Put on gloves • A gown is needed only when there is a risk of clothing or skin contamination (such as when examining young children who may have difficulty controlling their secretions) • Consider most appropriate respiratory protection 9/6/2009 249

Pandemic (H1N1) 2009 Triage Health Care Setting Guideline • BEFORE EVERY PATIENT CONTACT • Clean hands (wash with soap and water for at least 15 seconds or use alcohol gel/rub containing at least 60% alcohol) • Put on plastic apron/gown, surgical mask, gloves (and goggles if there is risk of exposure to splashes) • Change gloves and clean hands between patients and between care procedures • Clean and disinfect dedicated patient equipment between patients • IF USING AEROSOL‐GENERATING PROCEDURES – (e.g. intubation, bronchoscopy, CPR, suction) • Perform planned procedure in an adequately ventilated room • Allow entry of essential staff only • Clean hands • Put on long sleeved disposable gown • Put on particulate respirator mask (e.g. FFP2 or FFP3 –fit check to ensure a good seal) • Put on eye protection, and then put on gloves 9/6/2009 250

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Upon Arrival to clinical setting: • Follow instructions as listed in side panel: – ‘BEFORE EVERY PATIENT CONTACT’ • Direct patient with flu‐like symptoms to designated waiting area (fever, cough, headache, muscle pain, sore throat, runny nose, vomiting and diarrhoea) • Provide instruction and materials to patient on respiratory hygiene/cough etiquette and hand ‘BEFORE EVERY PATIENT hygiene CONTACT’ • Put surgical mask on patient if tolerable to patient • Ensure at least 1 metre(3 feet) between patients in cohort area 9/6/2009 A student has her temperature taken at 251 a swine flu clinic in Melbourne

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Upon Initial Assessment: • Record respiratory rate over one full minute and oxygen saturation if possible • If respiratory rate is high or oxygen saturation is below 90%, alert senior care staff for action • Record history, including flu‐like symptoms, date of onset, travel, contact with people who have flu‐like symptoms, co‐morbidities or conditions associated with high risk of complications • If taking Clinical Specimens: • Use surgical mask, plastic apron/gown, gloves (and goggles if risk of splashing or spraying) when taking respiratory samples • Take nose and throat viral swabs if admission is planned, and sputum for culture if it is indicated • Label specimen correctly and send to laboratory with biohazard precautions • Consider alternative or additional diagnoses 9/6/2009 252

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Initial and Ongoing patient Management: • Supportive therapy as for any influenza patient including: • Give oxygen to maintain oxygen saturation above 90% or if respiratory rate is elevated (when oxygen saturation monitor not available) • Administer antipyretics if required. If patient <16 years, aspirin is contraindicated • Ensure adequate fluid intake • Give appropriate antibiotic if evidence of secondary bacterial infection (e.g. pneumonia) • Consider alternative or additional diagnoses • Decide on need for antivirals (oseltamivir or zanamivir), considering contra‐indications and drug interactions using current guidance 9/6/2009 253

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Before Patient Transport/Transfer: • Put surgical mask on patient if tolerable to patient • Inform transferring staff of patient’s infectious status • Facilities should also ensure that plans are in place to communicate information about suspected cases that are transferred to other departments in the facility (e.g., radiology, laboratory) and other facilities 9/6/2009 254

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Before Patient Entry To Designated Area: • Post restricted entry and infection control signs • Provide dedicated patient equipment if available • Ensure at least 1 metre(3feet) between patients in cohort area • Patient charts/records should not be taken into the single room • Patient to wear surgical mask if outside isolation room or cohort area • Encourage pt to limit movement within facility • Ensure protocol for frequent linen change and surface cleaning in place • Patient to leave designated area only when essential 9/6/2009 255

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Visitors Entering Designated Area: – (isolation room or a cohorted area) – Schedule and control visits to allow for appropriate screening for acute respiratory illness before entering the hospital – Instruction on use of personal protective equipment and other precautions (e.g., hand hygiene, limiting surfaces touched) A nurse prepares an isolation ward and medical equipment, in the event – Visitors should be instructed to limit their movement that suspected Influenza A (H1N1) flu within the facility patients are hospitalised • Visitors should be restricted to a minimum • Clean hands • Put on surgical mask • On leaving designated area, remove mask outside room • Clean hands 9/6/2009 256

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Staff ‐Before Leaving Designated Area: – (isolation room or a cohorted area) • Remove gloves, clean hands, then remove goggles, gown/apron and dispose of as health care risk waste in room. Exit room, close door • Remove mask and dispose of as health care risk waste • Clean hands • Clean and disinfect dedicated patient equipment that has been in contact with patient • Dispose of viral‐contaminated waste as health care risk waste 9/6/2009 257

Pandemic (H1N1) 2009 Triage Health Care Setting Guidelines • Before Discharge: • Provide instruction and materials to patient/caregiver on respiratory hygiene/cough etiquette and hand hygiene • Provide advice on home isolation, infection control and avoiding social contact • Provide information about illness, follow up arrangements and take home medications • Provide advice to re‐consult if deterioration in condition 9/6/2009 258

Patient Resource for GPs Guidance For Caring For Persons At Home With Pandemic (H1N1) 2009 Influenza Virus Update : 26th, Aug, 2009 http://www.hpsc.ie/hpsc/A- 9/6/2009 Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfl 259 uenza/AdviceforHealthProfessionals/GPs/File,3636,en.pdf

Pandemic (H1N1)2009 Triage Health Care Setting Guidelines • After Discharge: • Dispose of or clean and disinfect dedicated patient equipment as per manufacturer’s instructions • Change and place laundry in an alginate bag and into a colour coded bag • Clean surfaces with detergent and disinfect using a hypochlorite solution 1000ppm Water soluble laundry bags for infection control in hospital • Dispose of viral‐contaminated waste as health care risk waste 9/6/2009 260

Pandemic (H1N1) 2009 “Patient Care Checklist Summary” http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealth 9/6/2009 Professionals/HospitalClinicians/File,3777,en.pdf 261

Pandemic (H1N1) 2009 Clinical Practice Note For Critical Care • Pandemic H1N1 2009 Clinical Practice Note • “Managing critically ill cases” http://www.hpa.org.uk/web/HPAwebFile/HPA 9/6/2009 web_C/1248854036293 262

Pandemic (H1N1) 2009 Diagnostics Summary • The following investigations are recommended “pandemic influenza expert group” in patients referred to hospital: Test Who this applies to Full blood count All patients Urea and electrolytes All patients Liver function tests All patients C-reactive protein If influenza-related pneumonia is suspected* Chest x-ray All patients Pulse oximetry All patients. If <92% on air, then arterial blood gases. ECG Patients with cardiac and respiratory complications or co-morbid illnesses. Patients with influenza-related pneumonia should also have the following bacteriological tests: Blood culture (Gold standard) preferably before antibiotic treatment is commenced Pneumococcal urine antigen 20 mls urine sample Legionella urinary antigen 20 mls urine sample Sputum Gram stain, culture Antimicrobial susceptibility tests on samples obtained from patients who: I. are able to expectorate purulent samples, and ii. are not received prior antibiotic treatment. Paired serological examination for influenza/other agents Acute serum should be collected and a ‘convalescent’ sample obtained after an interval 10-14 days (both 5-10mLs clotted blood) 9/6/2009 263

Clinical Management of Adults In The Hospital Setting • Severity assessment when presenting to hospital • Patients with uncomplicated influenza A(H1N1) infection would be expected to make a full recovery and do not require hospital care – Voluntary isolation with antivirals at home with self surveillance • Patients with worsening of pre-existing co-morbid medical conditions should be managed according to best practice for that condition with reference to published disease-specific guidelines (High risk groups) – Influenza-related Pneumonia assessment : • CURB-65 score* Bilateral pulmonary 9/6/2009 infiltrates 264

Clinical Management of an Adults In The Hospital Setting Management of Influenza-related Pneumonia • *Score 1 point for each feature present: • Confusion (Mental Test Score of ≤ 8, or new disorientation in person, place or time.) • Urea > 7mmol/L • Respiratory rate ≥ 30/min • Blood pressure (SBP < 90mmHg or DBP ≤ 60mmHg) Patient admitted to ICU with severe bilateral pneumonia • New bilateral lung shadowing on CXR consistent with primary viral pneumonia should be taken as a feature of severe pneumonia regardless of CURB-65 score! • Assessment of those with Influenza-related pneumonia: • Severity assessment: (CURB-65 score) – *Score 1 point for each feature present CURB-65 score* Recommended action 0 Likely suitable for home treatment 1 or 2 Consider elective hospital stay, particularly with score 2, or hospital supervised outpatient stay 3 or more Manage in acute hospital as severe pneumonia 9/6/2009 265

Clinical Management of Adults In The Hospital Setting • High Dependency or Intensive Care Unit referral: • Patients with primary viral pneumonia or a CURB-65 score of 4 or 5 should be considered for HDU/ICU referral • General indications for HDU/ICU referral include: 1. Persisting hypoxia with PaO2 <8Kpa despite maximal oxygen administration 2. Progressive hypercapnia 3. Severe acidosis (pH<7.26) 4. Septic shock 9/6/2009 266

Paediatric Respiratory Distress Severity Assessment Paediatric Respiratory Distress Mild Severe Severity Assessment Infants Temperature ≥38.5 °C Temperature ≥38.5 °C Respiratory rate <50 breaths per min Respiratory rate >70 breaths per min Mild recession Moderate to severe recession Taking full feeds Nasal flaring Infants Cyanosis Intermittent apnoea Grunting respiration Not feeding Older children Temperature > 38.5 °C Temperature > 38.5 °C Resp rate < 50 breaths per min Resp rate > 50 breaths per min Mild breathlessness Severe difficulty in breathing No vomiting Nasal flaring Cyanosis Grunting respiration 9/6/2009 Signs of dehydration 267

Clinical Management of Children Presenting To Hospital • Coughs and mild fevers: – Treat at home by parents with antipyretics and fluids – (Note: aspirin should not be used in children < 16 years) • High fever (≥ 38.5°C /101.3°F) and cough or influenza like symptoms : – Seek medical advice • If there are no features which put them at high risk of complications they should be treated with oseltamivir, and given advice on antipyretics and fluids • Children at risk of complications, and all children aged less than 5 years should be seen by a GP • High fever (≥ 38.5°C /101.3°F) and cough or influenza like symptoms PLUS at-risk group. These children should be seen by their GP or in an Emergency Department • Children may be considered at increased risk of complications if they have cough and fever (or influenza like illness) and temperature ≥ 38.5°C/101.3°F AND either chronic disease or one of following features: – Breathing difficulties – Severe earache – Vomiting > 24 hours – Drowsiness 9/6/2009 268

Clinical Management of Children Presenting To Hospital • Criteria for hospital referral for admission are any of the following: 1. Signs of persistent respiratory distress – markedly raised respiratory rate – grunting – intercostal recession – breathlessness with chest signs 2. Cyanosis 3. Severe dehydration 4. Altered conscious level 5. Complicated or prolonged seizure 6. Signs of septicaemia – extreme pallor, hypotension, floppy infant 7. Most children admitted to hospital are likely to need oxygen therapy and/or intravenous support as well as antibiotics and oseltamivir • Assess for: • Influenza-like Illness (ILI) • Severs respiratory illness with suspected/probable pneumonia (SRI) • Acute Respiratory Distress Syndrome (ARDS)…..leading to multi-organ failure 9/6/2009 269

Clinical Management of Children Presenting To Hospital • Indications for referral to High Dependency or Intensive Care are: 1. The child is failing to maintain a SaO2 of >92% in FiO2 of >60% 2. The child is in shock 3. There is severe respiratory distress and a raised PaCO2 ( > 6.5 Kpa) 4. There is a rising respiratory rate and pulse rate with clinical evidence of severe respiratory distress with or without a raised PaCO2 5. There is recurrent apnoea or slow irregular breathing 6. There is evidence of encephalopathy 9/6/2009 270

Clinical Management of Children Presenting To Hospital • Microbiological/virological investigations in hospital: – WHO Phase 6, Irish Alert levels 2 and 3) • A. Virology – all children – Nasopharyngeal aspirate or nose and throat swabs – If presentation is more than 7 days after onset of illness, an ‘acute’ serum (2-5 ml clotted blood) should be collected and a ‘convalescent’ sample (2- 5 ml clotted blood) obtained after an interval of not less than 7 days • B. Bacteriology – children with influenza related pneumonia – Blood culture (before antibiotic treatment is commenced) – Sputum samples obtained from older children – Paired serological examination for influenza/other agents 9/6/2009 271

Pandemic (H1N1) 2009 Virus Clinical Management : Discharge Check list • Discharge and follow up Children can be safely discharged – Patients should be reviewed 24 from hospital when they: hours prior to discharge home – Are clearly improving – Are physiologically stable • Those with 2 or more of the – Can tolerate oral feeds following unstable clinical factors – Have a respiratory rate <40/min ( should be considered for <50/min in infants) continuing care in hospital: – Have an awake oxygen saturation of < 92% in air – Temperature ≥37.8°C – Heart rate >100/min – Respiratory rate > 24/min Follow up clinical review should be considered – Systolic blood pressure <90mmHg for all patients who suffered significant – Oxygen saturation < 92% on room complications or who had significant worsening air of their underlying disease, either with their – Inability to maintain oral intake general practitioner or in a hospital clinic. – Abnormal mental status or mental status not returned to baseline. 9/6/2009 272

Pandemic (H1N1) 2009 Virus Clinical Management :Hospital and Community Setting Resource Extensive clinical Practice Guidelines are available at this Hyperlink (Click during Slide show!) • http://www.ndsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPande micInfluenza/Guidance/PandemicI nfluenzaPreparednessforIreland/Fil e,3261,en.pdf 9/6/2009 273

High Risk Group HPA Algorithm for Pregnancy 9/6/2009 Awaiting for one from HPSC! 274

High Risk Group Algorithm for Asthmatics • Call for “Asthmatic” and “Bariatric” Algorithms for influenza! • Please contact Michael Fraser at – michaelfraser.ifpri@gmail.com “We will develop a clinical pathway/care bundle in the mean time with local resources and compare other algorithms for improvements!” Will be available September, 15, 2009 update! 9/6/2009 275

HPSC References for Patient Care Checklist for Hospitals as of July, 29, 2009 • 28th July 2009, Version 2.0 • 1. Respiratory Hygiene and Cough Etiquette Poster • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/InfectionControl/File,3599 ,en.pdf • 2. Guidance on hand hygiene • http://www.ndsc.ie/hpsc/A‐Z/Gastroenteric/Handwashing • 3. Pandemic Influenza Preparedness for Ireland: Advice of the Pandemic Influenza Expert Group, Chapter 9, Appendix 1 • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/Guidance/PandemicInfluenzaPreparednessforIreland/File,3261,en.pdf • 4. Taking specimens for influenza virus testing from patients with suspected influenza A(H1N1) • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/LaboratoryTesting/File,38 86,en.pdf • 5. Algorithm for the management of persons with acute febrile respiratory illness who may have influenza A(H1N1) • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/HospitalClinicians/File,358 5,en.pdf • 6. Infection Prevention and Control Guidance for the Ambulance Service for suspected or confirmed cases of Influenza A(H1N1) • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/AmbulanceStaff/File,3601 ,en.pdf • 7. Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Influenza A(H1N1) • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/InfectionControl/File,3628 ,en.pdf • 8. Donning and Removing Personal Protective Equipment (PPE) • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/InfectionControl/File,3627 ,en.pdf • 9. Aerosol Generating Procedures • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/InfectionControl/File,3625 ,en.pdf • 10. Taking care of a sick person with Flu • http://www.hpsc.ie/hpsc/A‐Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdvicefortheGeneralPublic/File,3660,en.pdf • See HPSC website for download, • Recommended to have a staff member assigned to check for, and download updates !

Pandemic (H1N1) 2009 Clinical Diagnostics 9/6/2009 277

Guidance on Laboratory procedures when pandemic influenza is present outside Ireland (Irish Alert Level 2) • Containment stage: Samples should be collected for influenza investigation (including viral culture when advised by GP ) from all patients who: 9/6/2009 278

Specimens for Influenza Virus Testing for Treatment Phase • New testing Policy As of July ,29, 2009 • “The current swabbing policy is amended so that testing is only necessary in the following circumstances: • Cases hospitalised for influenza • Cases identified via the GP sentinel surveillance scheme • Other situations, following discussion with local public health – for example: – Cases of influenza like illness (ILI) in an institution – Unusual clusters of serious illness – Influenza like illness (ILI) or unexplained illness occurring in a hospitalised patient – Development of influenza like illness (ILI) in a person on chemoprophylaxis” http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfl uenza/SwineInfluenza/AdviceforHealthPr ofessionals/GPs/File,3869,en.pdf 9/6/2009 279

Taking Specimens for Influenza Virus Testing From Patients with Suspected Pandemic (H1N1) 2009 Virus • Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie • See Website for download for clinicians or hyperlink during slideshow http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPand emicInfluenza/SwineInfluenza/Ad viceforHealthProfessionals/Hospit alClinicians/File,3604,en.pdf 9/6/2009 280

Pandemic (H1N1) 2009 Virus Irelands Laboratories Overview • Approximately 34 (BL3) laboratories distributed among the universities an biotechnology companies in Ireland • These predominantly handle up to Category 3 pathogens or conduct genetic manipulations under regulation of the Environmental Protection Agency • High containment Class 3 (+) laboratory has been commissioned at the University College Dublin National Virus Reference Laboratory (UCD NVRL) • Environmental and clinical specimens are investigated in a Class 3 containment laboratory at Cherry Orchard Hospital, Dublin • Novel Influenza A H1N1 in BSL-3 practices (enhanced BSL-2 conditions) 9/6/2009 281

Pandemic (H1N1) 2009 Influenza National Virus Reference Laboratory • Postal address: Medical Microbiology, CRID Building, University College Dublin, Belfield, Dublin 4, Ireland. Telephone Number: +353-1-716 1325/1236 Fax Number: +353-1-716 1239 Email: margaret.brindley@ucd.ie 9/6/2009 282

Pandemic (H1N1) 2009 Virus Specimen Collection • Clinicians should obtain a respiratory swab for swine influenza testing and place it in a refrigerator (not a freezer). – A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab) – Collected during the first five days • Once collected, the clinician should contact their state or local health department to facilitate transport and timely diagnosis at a public health laboratory • Laboratories should send all unsubtypable influenza A specimens as soon as possible to NRVL • Spill containment measures should be in place! 9/6/2009 283

Pandemic (H1N1) 2009 Influenza Laboratory Precautions • Viral isolation on clinical specimens from patients who are suspected cases of swine influenza A (H1N1) virus infection should be performed in a BSL2 laboratory with BSL3 practices (enhanced BSL2 conditions) • Additional precautions include: Recommended Personal Protective Equipment (based on site specific risk assessment ) – Respiratory protection – fit-tested FFP 2-3 respirator or higher level of protection – Shoe covers – Closed-front gown – Double gloves – Eye protection (goggles or face shields) 9/6/2009 284

Pandemic (H1N1) 2009 Influenza Laboratory Precautions • Routine laboratory procedures, including diagnostic work and PCR analysis: • Biosafety Level 2 (BSL2), as detailed in the WHO Laboratory biosafety manual, 3rd edition. • Examples of routine laboratory procedures that require BSL2 include: • Diagnostic testing of serum, blood (including haematology and clinical chemistry), respiratory tract specimens, or other specimens • Manipulations involving neutralized or inactivated (lysed, fixed, or otherwise treated) virus particles and/or incomplete, non-infectious portions of the viral genome • Routine examination of mycotic and 9/6/2009 285 bacterial cultures

Pandemic (H1N1) 2009 Influenza Laboratory Precautions • Viral isolation on clinical specimens from patients who are suspected or confirmed cases of Pandemic Influenza A(H1N1) 09 Virus infection should only be performed in laboratories capable of meeting the following additional essential (minimal) Bio containment :BL3(+) Two microbiological safety cabinets containment requirements: (msc ) class I and class I/ III) at • Practices recommended for NVRL containment laboratories — Biosafety Level 3 in the WHO Laboratory biosafety manual, 3rd edition 9/6/2009 286

Pandemic (H1N1) 2009 Virus Laboratory Precautions • A controlled ventilation system maintains directional airflow into the laboratory room • Exhaust air from the laboratory room is not recirculated to other areas within the building – Air should be HEPA filtered, if reconditioned NRVL BL3(+) Has and recirculated within the laboratory. two microbiological – When exhaust air from the laboratory is safety cabinets (class discharged to the outdoors, it must be I and class I/ III) dispersed away from occupied buildings and air intakes. – This air may be discharged through HEPA filters • All manipulations of infectious or potentially infectious materials must be performed in appropriately maintained and validated BSCs. (Ireland: NRVL Uses msc class I and class I/ III) • Access to the laboratory is restricted when work is in progress 9/6/2009 287

Pandemic (H1N1) 2009 Virus Laboratory Precautions • Viral isolation on clinical specimens : • Biosafety Level Three plus (BL3+) containment laboratory • PPE • Laboratory workers should wear protective equipment, including: – Disposable gloves NRVL Layout of Bio – Solid front or wrap-around gowns Containment :BL3(+) – Scrub suits – Coveralls with sleeves that fully cover the forearms – Head coverings – Shoe covers or dedicated shoes – Eye protection (goggles or face shield) – Respiratory protection (fit-tested particulate respirator, e.g. EU FFP2, US NIOSH-certified N95 or equivalent, or higher protection), because of the risk of aerosol or droplet exposure 9/6/2009 288

Pandemic (H1N1) 2009 Virus Laboratory Precautions Summary • Clinical laboratory testing • Viral isolation (laboratory diagnostic work) • Diagnostic laboratory work on • Growth of the virus in cell culture clinical samples from patients or embryonated eggs should be who are suspected cases of novel performed in a BSL-2 laboratory influenza A H1N1 virus infection with BSL-3 practices. should be conducted in a • All viral manipulations should be biosafety level 2 (BSL-2) done inside a microbiological laboratory. safety cabinets (msc ) class I and • All sample manipulations with class I/ III) that is certified the potential for creating an annually. aerosol should be done inside a microbiological safety cabinets (MSC) that is certified annually. Bio containment :BL3(+) Two microbiological safety cabinets (msc ) class I and class I/ III) at NVRL 9/6/2009 289

Pandemic (H1N1) 2009 Influenza Laboratory Precautions • Animal work • The following activities require animal facility — Biosafety Level 3 facilities and work practices, as detailed in the WHO Laboratory biosafety manual, 3rd edition. – Inoculation of animals for potential recovery of the agent from influenza A (H1N1) specimens – Any protocol involving animal inoculation for confirmation and/or characterization of putative influenza A (H1N1) agents – Bio containment :BL3(+) At NRVL/Cherry Orchard 9/6/2009 290

Pandemic (H1N1) 2009 Influenza Laboratory Precautions • Waste • All waste disposal procedures should be followed as outlined in your facility standard laboratory operating procedures • Appropriate disinfectants • 70% Ethanol • 5% Lysol • 10% Bleach • Influenza viruses can survive on environmental surfaces and can infect a person for up to 2 to 8 hours after being deposited on an environmental surface • Commonly used surfaces such as door handles, handrails, table surfaces etc. should be cleaned first and then disinfected with a chlorine releasing disinfectant (1000 ppm) twice daily Detailed information on • Disinfectants with proven activity against enveloped viruses disinfectants and their recommended use can be include chlorine, alcohol, peroxygen, quaternary ammonium found in Laboratory biosafety manual, 3rd compounds and phenolic compounds and should be adequate if ed., Geneva, World Health Organization, 2004 used according to manufacturer’s recommendations 9/6/2009 291

Pandemic (H1N1) 2009 Virus Laboratory Precautions • Personnel should self monitor for fever and any symptoms Never place knee on • Accidental exposure: floor – Antiviral chemoprophylaxis with zanamivir or oseltamivir for 7 days( See PEP slide) Centre for Disease Control and Prevention, shows a negative-stained image of the swine flu virus. 9/6/2009 292

NRVL Testing for Pandemic (H1N1) 2009 Virus • Preferred Respiratory Specimens • Swabs – Nasopharyngeal Aspirates • Recommended Tests • Other Influenza Tests HSE :Taking specimens for – Rapid Influenza Antigen Test influenza virus testing from patients with – Immunofluorescence (DFA or IFA) suspected Pandemic Influenza A(H1N1) 09 – Viral Culture Virus 9/6/2009 293

NRVL Testing for Pandemic (H1N1) 2009 Influenza • Taking specimens for influenza virus testing from patients with suspected influenza A (H1N1): • As with all respiratory viruses, diagnosis of influenza virus depends on the collection of high-quality specimens, their rapid transport to the virology laboratory and appropriate storage before laboratory testing • Virus is best detected in specimens containing infected cells and secretions • Specimens should ideally be taken preferably during the first 5 days after onset of clinical symptoms 9/6/2009 294

NRVL Testing for Pandemic (H1N1) 2009 Influenza • Before taking specimens: • Before a specimen is taken, it should first be reviewed as outlined in the national algorithms for the management of persons with possible pandemic influenza A(H1N1) 09 virus • Infection prevention and control precautions – While not strictly an aerosol generating procedure it is recommended that the same precautions are followed when taking nasal and throat viral swabs to out rule influenza A(H1N1) 09 virus (Do risk assessment) 9/6/2009 295

NRVL Testing for Pandemic (H1N1) 2009 Influenza • Infection prevention and control precautions: • While not strictly an aerosol generating procedure it is recommended that the following PPE is used when taking nasal and throat viral swabs to out rule influenza A (H1N1) • The following personal protective equipment (PPE) should be taken: – Hand hygiene – Standard Precautions – Surgical – Eye protection (i.e. goggles) – Plastic apron (single use only) – Gloves (some of these procedures require sterile gloves) – Hand hygiene post procedure • Refer to donning and removal of PPE document 9/6/2009 296

Aerosol Generating Procedures (AGP) According to WHO And HPSC • Aerosol generating procedures: • Nebulisation • Intubation and related • Non-invasive positive procedures, e.g. manual pressure ventilation(NIV) ventilation • Bi-level positive airway • Respiratory and airway suctioning pressure (BiPAP) ,CPAP, (including tracheostomy care) • High frequency oscillating • Nasopharyngeal aspiration ventilation • Cardiopulmonary resuscitation • Bronchoscopy • Nasopharyngeal aspirate • Transtracheal aspirate • Bronchoalveolar lavage • Biopsy of lung or tracheal tissues • Autopsy procedures – i.e.. (Oscillating saws) 9/6/2009 297

Pandemic (H1N1) 2009 Influenza Infection Prevention and Control Precautions Personal Protective Equipment (PPE) Summary • Nasal and throat viral swabs: • Nasopharyngeal aspirate, transtracheal aspirate, • The following precautions should be bronchoalveolar lavage and biopsy taken: of lung or tracheal tissues at post- mortem, nebulizers , • Hand hygiene BIPAP/CPAP/NIV are all considered • Surgical mask aerosol generating procedures: • Goggles (if risk of splashing or spraying) • The following precautions should be • Plastic apron taken: • Gloves • Hand hygiene • Hand hygiene post procedure • FFP2 or FFP3 respiratory mask • Goggles • Long sleeved disposable gown • Gloves (some of these procedures require sterile gloves) • Hand hygiene post procedure Update June 9 2009 9/6/2009 298

Point of Care Risk Assessment Tool for Pandemic (H1N1) 2009 Influenza • Point of Care Risk Assessment (PCRA) is an activity performed by the HCW before every patient interaction, to: • Rational: • Evaluate the likelihood of exposure to H1N1 2009 – From a specific interaction (e.g., performing/ assisting with aerosol-generating medical procedures, other clinical procedures/ interaction, non-clinical interaction (i.e., admitting, teaching patient/ family), transporting patients, direct face-to-face interaction with patients, etc.), – With a specific patient (e.g., infants/ young children, patients not capable of self care/ hand hygiene, have poor-compliance with respiratory hygiene, copious respiratory secretions, frequent cough/ sneeze, early stage of influenza illness, etc.), – In a specific environment (e.g., single rooms, shared rooms/ washrooms, hallway, influenza assessment areas, emergency departments, public areas, therapeutic departments, diagnostic imaging departments, housekeeping, etc.), – Under available conditions (e.g., air exchanges in a large waiting area or in an airborne infection isolation room, patient waiting areas); • And • Choose the appropriate actions/ PPE needed to minimize the risk of patient, HCW/ other staff, visitor, contractor, etc. exposure to H1N1 2009 /suspect ILI case

NRVL Testing for Pandemic (H1N1) 2009 Influenza • Respiratory specimens to take: • A. Upper respiratory tract – Nasopharyngeal (NP) and oropharyngeal (OP) swab – Nasopharyngeal aspirate – Sputum (if ordered) • B. Lower respiratory tract – Where clinically indicated, invasive procedures can be performed for the diagnosis of viral lower respiratory tract infections: – Transtracheal aspirate (TA) – Bronchoalveolar lavage (BAL) – Post-mortem lung or tracheal tissue 9/6/2009 300

NRVL Testing for Pandemic (H1N1) 2009 Influenza • Swabs to use: – Specific viral swab (contains viral transport medium in the container of the swab) – Regular swab – after taking the specimen the swab should be broken off into a bottle containing virus transport medium – Nasopharyngeal secretions should be aspirated into a sterile plastic mucous extractor. Transport the mucous extractor with the secretions – A transtracheal aspirate/ bronchoalveolar lavage should be transported in a sterile container 9/6/2009 301

Pandemic (H1N1) 2009 Influenza Nasopharyngeal Swabs • According to PHAC And CDC : Nasopharyngeal Swabs • Ideally, swab specimens should be collected using (COPAN flocked swab) swabs with a synthetic tip (eg, polyester or Dacron) and a plastic shaft • Optimal specimens continue to be Nasopharyngeal Swabs (COPAN flocked swab) but Starplex non- flocked swabs are also acceptable for nasopharyngeal and nasal samples • Do not use wired shaft pertussis swab as it interferes with the test and give a false negative result • Swabs with cotton tips and wooden shafts are not recommended • Specimens collected with swabs made of calcium alginate are not acceptable • The swab specimen collection vials should contain 3 mL of VTM (eg, containing protein stabilizer, antibiotics to discourage bacterial and fungal growth, and buffer solution), such as M4RT or the BD Universal Viral Transport System 9/6/2009 302

Pandemic (H1N1) 2009 Influenza Flocked Swabs and Copan-Manufactured VTM for Pandemic Influenza A(H1N1) 09 Virus • CDC Recommends Flocked Swabs and Copan-Manufactured VTM for H1N1 Pandemic Influenza A(H1N1) 09 Virus : Optimal specimens continue to be Nasopharyngeal Swabs (COPAN flocked swab) NP Swab Animation 9/6/2009 303

Pandemic (H1N1) 2009 Influenza Nasopharyngeal Flocked Swabs Procedure • “Specimens for the laboratory diagnosis of Pandemic (H1N1)2009 Influenza virus should be collected in the following order of priority: 1. Nasopharyngeal aspirates 2. Acute serum 3. Convalescent serum Paediatric Procedure 9/6/2009 304

Pandemic (H1N1) 2009 Influenza Nasopharyngeal (NP) , Oropharyngeal (OP) Swab • Nasopharyngeal (NP) and oropharyngeal (OP) swab collection: • Collect specimen with a sterile Dacron/nylon swab with a non-wooden shaft (do NOT use calcium alginate swabs or swabs with wooden sticks) • For NP swab, insert swab into each nostril parallel to the palate and leave in place for a few seconds to absorb secretions. Swab both nostrils • For OP swab, swab the posterior pharynx and tonsillar areas, avoiding the tongue • Place swab immediately into sterile vials containing 2 ml of viral transport media • Label each specimen container with patient’s FIRST AND LAST NAME, date of birth, medical record number, date of collection, specimen type • Place specimen vial onto ice or in refrigerator prior to and during transport at 4°C (but not frozen) • Should not be kept un-refrigerated for more than 12 hours 9/6/2009 305

Pandemic (H1N1) 2009 Influenza Nasopharyngeal Aspirates Overview • Ideally, swab specimens should be collected using swabs with a synthetic tip (eg, polyester or Dacron) and an aluminium or plastic shaft • Swabs with cotton tips and wooden shafts are not recommended • Specimens collected with swabs made of calcium alginate are not acceptable • The swab specimen collection vials should contain 3 ml of VTM (eg, containing protein stabilizer, antibiotics to discourage bacterial and fungal growth, and buffer solution), such as M4RT or the BD Universal Viral Transport System 9/6/2009 306

Pandemic (H1N1) 2009 Influenza Nasopharyngeal Aspirates Procedure • Hierarchy “Specimens for the laboratory diagnosis of Novel A (H1N1)Influenza should be collected in the following order of priority: 1. Nasopharyngeal aspirates 2. Acute serum 3. Convalescent serum 9/6/2009 307

Pandemic (H1N1) 2009 Influenza Nasopharyngeal Aspirates Collection • Nasopharyngeal wash/aspirates collecion: • Have the patient sit with head tilted slightly backward • Instill 1ml-1.5ml of nonbacteriostatic saline (pH 7.0) into one nostril • Insert the tubing into the nostril parallel to the palate • Aspirate nasopharyngeal secretions. Repeat this procedure for the other nostril • Rinse the catheter into viral transport medium (syringe or bulb) or aspirate viral transport media through catheter into collection trap • Label specimen container with patient’s FIRST AND LAST NAME, date of birth, medical record number, date of collection, specimen type • Place specimen vial onto ice or in refrigerator prior to and during transport • Do not freeze 9/6/2009 308

Pandemic (H1N1) 2009 Influenza Bronchoalveolar Lavage (BAL) Collection • Bronchoalveolar lavage or tracheal aspirate: • During bronchoalveolar lavage or tracheal aspirate, use a double-tube system to maximize shielding from oropharyngeal secretions • Centrifuge half of the specimen, and fix the cell pellet in formalin • Place the remaining unspun fluid in sterile vials with external caps and internal O-ring seals • If there is no internal O-ring seal, then seal tightly with the available cap and secure with Parafilm® • HPSC ; broncheoalveolar lavage should be transported in a sterile container 9/6/2009 309

Pandemic (H1N1) 2009 Influenza Sputum Collection • Sputum collection: • Educate the patient about the difference between sputum and oral secretions • Have the patient rinse the mouth with water and then expectorate deep cough sputum directly into a sterile screw-cap sputum collection cup or sterile dry container • Label specimen container with patient’s FIRST AND LAST NAME, date of birth, medical record number, date of collection, specimen type • Place specimen vial onto ice or in refrigerator prior to and during transport • Do not freeze 9/6/2009 310

Pandemic (H1N1) 2009 Virus Stool Collection • In the USA, gastrointestinal symptoms (nausea, vomiting and/or diarrhoea) have occurred in up to 38% of outpatients with confirmed influenza A(H1N1) • Diarrhoea has been uncommon in hospitalised cases • SOP (Standard operating procedure) on collection • Full PPE (in case of splashes) • Place in Biological Bag • Do not freeze! • For all specimens Contact DPH/MOH/NVRL for shipping instructions accordance to national and international standards 9/6/2009 311

Pandemic (H1N1) 2009 Influenza Serology Suites • Acute Serum Suites • Convalescent Serum Suites • Immediate • 14 days after • Specimens: • Specimens: – Blood in clotted tube (red top) – Blood in clotted tube (red top) – Blood in EDTA (purple top) – Blood in EDTA (purple top) • {Full blood count) – {Full blood count) • Additional routine blood work according to physicians orders or follow pre ordered Influenza-like illness ,Influenza A(H1H1) suites as institutional protocols 9/6/2009 312

Pandemic (H1N1) 2009 Virus Serology Acute and Convalescent Serum Samples • Acute and Convalescent serum samples: • Collect 5-10 ml whole blood in a serum separator or red top tube Allow the blood to clot, centrifuge briefly, and collect all resulting sera in vial with external caps and internal O-ring seals • Refrigerate at 4°C • The minimum amount of serum needed for testing is 5 ml of whole blood • A minimum of 1 cc of whole blood is needed for testing of paediatric patients • If possible, collect 1 cc in an EDTA tube and in a clotting tube • If only 1 cc can be obtained, use a clotting tube • Label specimen container with patient’s FIRST AND LAST NAME, date of birth, medical record number, date of collection, specimen type 9/6/2009 313

Pandemic (H1N1) 2009 Influenza and Blood Safety • 2009 H1N1 Influenza Virus and Blood Safety: • Bld cultures Aerobic No case of transfusion transmitted seasonal influenza has ever then anaerobic been reported in the United States or elsewhere, and, to date, no cases of transfusion transmitted H1N1 flu have been reported! • Safety of Plasma Derivatives • The newly emerging 2009 H1N1 Influenza Virus is a large lipid- enveloped virus. Validation studies performed by the product manufacturers have shown that viruses with similar characteristics to this agent are effectively inactivated and/or removed by the manufacturing processes in place for these products • Individuals who are not in good health are not suitable to donate blood and blood establishments must defer these potential donors therefore…. • Blood donor screening procedures currently in place at blood establishments should identify persons with symptoms of H1N1 flu infection 9/6/2009 314

Pandemic (H1N1) 2009 Influenza and Blood Safety • Irish Blood Transfusion Service advisory • Swine Flu Important Information • “We are asking all donors who have returned from Mexico or the United States of America in the last 14 days NOT to attend any blood donor clinic at this time. This situation is under review on a daily basis and further updates will be available here. Please note that this precaution is in the interest of donor and recipient safety. Your patience and cooperation is greatly appreciated” 9/6/2009 315

Pandemic (H1N1) 2009 Influenza Diagnostics - Chest X-ray • Approximately 2-5% of confirmed cases in the US and Canada as well as 6% in Mexico have been hospitalised • In Mexico – One-third of those hospitalised required mechanical ventilation • Of those hospitalised in California – 15 of 25 (60%) tested had radiographic changes suggestive of pneumonia including ten with multilobar infiltrates – Four (13%) required mechanical ventilation 9/6/2009 316

Pandemic (H1N1) 2009 Influenza Diagnostics Summary • The following investigations are recommended in patients referred to hospital: Test Who this applies to Full blood count All patients Urea and electrolytes All patients Liver function tests All patients C-reactive protein If influenza-related pneumonia is suspected* Chest x-ray All patients Pulse oximetry All patients. If <92% on air, then arterial blood gases. ECG Patients with cardiac and respiratory complications or co-morbid illnesses. Patients with influenza-related pneumonia should also have the following bacteriological tests: Blood culture preferably before antibiotic treatment is commenced Pneumococcal urine antigen 20 mls urine sample Legionella urinary antigen 20 mls urine sample Sputum Gram stain, culture Antimicrobial susceptibility tests on samples obtained from patients who: I. are able to expectorate purulent samples, and ii. are not received prior antibiotic treatment. Paired serological examination for influenza/other agents Acute serum should be collected and a ‘convalescent’ sample obtained after an interval not less than 7days (both 5-10mLs clotted blood) 9/6/2009 317

Pandemic (H1N1) 2009 Influenza Virus Real-time RT-PCR Detection Panel (Swine Flu Test Kit) • Countries with the PCR Capacity in Place to Diagnose Pandemic Influenza A(H1N1) 09 virus Infection in Humans Doc Available at WHO • 23 EU and EFTA countries are currently able to perform PCR to diagnose Pandemic Influenza A(H1N1) 09 virus infection in humans 9/6/2009 318

Pandemic (H1N1) 2009 Influenza Laboratory Tests Molecular Diagnostics: • Molecular diagnostics: • S-OIV assay The swine-origin influenza virus (S-OIV) assay (National Virus Reference Laboratory, NVRL, Dublin) is a real-time one-step RT-PCR assay containing primers and a dual-labelled hydrolysis probe targeting the M gene of influenza A viruses other than seasonal A(H1N1) and A(H3N2) viruses • HPA (H1)v assay The influenza A(H1)v specific assay of the Health Protection Agency (HPA) contains primers and a dual-labelled TaqMan MGB probe (Applied Biosystems) targeting conserved sequences in the HA gene of A(H1N1)v viruses, and the positive control swine A(H1N1) virus A/Aragon/3218/2009, in a 1-step TaqMan PCR assay [3]. The advantage of using a genetically distinct positive control virus (A/Aragon/3218/2008) is that false positives can be differentiated by sequence from true positives • CDC (H1)v assay The Centers for Disease Control and Prevention (CDC) real-time RT-PCR kit designed for the detection and characterisation of influenza A(H1N1)v viruses contains a panel of oligonucleotide primers and dual-labelled hydrolysis probes [4]. The CDC (H1)v primer and probe set evaluated in this study has been designed to specifically detect A(H1)v influenza in a one-step RT-PCR assay. • HPA (N1)v assay The influenza A(N1)v real-time assay (HPA) is a two-step TaqMan PCR assay incorporating oligonucleotide primers and a dual-labelled MGB TaqMan probe for the detection of the NA gene of influenza A(H1N1)v viruses and the positive control virus A/Aragon/3218/2008 [5]. The assay has been designed to be performed in conjunction with the influenza A(H1)v specific assay, to provide confirmation of diagnosis of influenza A(H1N1)v virus infection 9/6/2009 319

Swine Influenza Virus Real-time RT-PCR Detection Panel (Swine Flu Test Kit) • Instructions how to obtain CDC real time RT-PCR Kits for detection of Influenza A( H1 N1) • Thr rRT-PCR kits includes the following primers /probes: – Universal Influenza A(Infa) – Swine Influenza A(swIfa) – SwineH1 (swH1) – RNaseP (Control)( RP) • The rRT-PCR kits can also include detailed procedures CDC-developed PCR as well as positive control materials diagnostic test to detect novel H1N1 virus • Send the following e-mail to flouder@cdc.gov • I would like to request a rRT-PCR primers/probe kit for Swine A/H1 Flu • Contact name: • Institution Name: • Contact phone #: • 9/6/2009 Institution Shipping Address(No PO Box): 320 • Preferred Shipping carrier:

Pandemic (H1N1) 2009 Virus Virus Real-time RT-PCR Detection Panel • INTENDED USE: The Influenza A(H1N1) Virus Real-time RT-PCR Detection Panel is intended for use in real- time RTPCR assays on an ABI 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information • Test from nasopharyngeal or nasal swab BinaxNOW® Real-time PCR Biosystems 7500 Influenza A & B detection of Mexican Real-Time PCR Test Swine Flu Kit A C B 9/6/2009 321

Pandemic (H1N1) 2009 Influenza Laboratory Tests • Real-time RT-PCR for influenza A, B, H1, H3 – swine-origin influenza A (H1N1) virus will test positive for influenza A and negative for H1 and H3 by real-time RT-PCR • Rapid influenza antigen test • Immunofluorescence (DFA or IFA): • Viral culture: • Please Read below in narration! • Emergency Use Authorization of Swine Flu Test Kit : NML Winnipeg • Centers for Disease Control and Prevention (CDC) has developed the Swine Influenza Virus Real-time RT-PCR Detection Panel (Swine Flu Test Kit) for the presumptive presence of swine influenza A (H1N1) virus from the nasal or nasopharyngeal swab. • Swine Influenza Test Kit will be made available on the CDC Swine Flu website. 9/6/2009 322

Pandemic (H1N1) 2009 Influenza Recommended Tests • Real-time RT-PCR for influenza A, B, H1, H3 at a state health department laboratory is recommended • Currently, Pandemic Influenza A(H1N1) 09 Virus will test positive for influenza A and negative for H1 and H3 by real-time RT-PCR • If reactivity of real-time RT-PCR for influenza A is strong (eg, Ct <30), it is more suggestive of a novel influenza A virus • Confirmation of Novel Influenza is performed at the NRVL currently, but may be available in public health laboratories 9/6/2009 323

CDC Rt-PCR Testing Algorithm and Results Interpretation The overall approach to influenza virus detection by RT-PCR should be considered in the context of the national situation, e.g., how many swl = swine like specimens can be handled (throughput), what gene sequence to target for RT-PCR, and whether to use concurrent or sequential testing for RT-PCR of PCR Assays AIV = Avian Influenza virus M, NP and HA genes. PCR = Polymerase chain reaction Influenza A-swl subtype specific Influenza type A (universal) PCR (H1 gene) Matrix gene PCR (other genes targets are optional) Test for Seasonal influenza H1-and N3 using specific Confirmed Positive Positive Positive PCR H1N1 swl And tested negative Positive Negative for seasonal influenza H1 or H3 specific PCR Check for lab Negative Positive confirmation by Influenza A Negative retesting from original Other than H1N1 swl sample Negative for influenza A viruses (check for Positive Check for lab other pathogens confirmation by Positive retesting from original Negative Confirmed Positive sample Test for H5N1 or other AIV or H1 or H3 Influenza B 9/6/2009 324

Submission of Tissue Specimens for the Pathologic Evaluation of Pandemic (H1N1) 2009 Influenza • Central (hilar) lung with segmental bronchi, right and left primary bronchi, trachea (proximal and distal) • Representative pulmonary parenchyma from right and left lung • For patients with suspected myocarditis, encephalitis, or rhabdomyalysis, myocardium (right and left ventricle), central nervous system (cerebral cortex, basal ganglia, pons, medulla, and cerebellum), and skeletal muscle, respectively • Any other organ showing significant gross or microscopic pathology 9/6/2009 325

Pandemic (H1N1) 2009 Influenza Submission of Specimens • General Guidelines for Shipping Pathology Specimens: • Packaging and Shipping Guidelines Layout of Bio Containment :BL3(+) – Formalin-fixed wet tissues OL: Outer lobby S: Shower – Formalin-fixed paraffin- IL: Inner Lobby LAB: Laboratory embedded blocks – Glass slides with sections from paraffin-embedded blocks – Fresh frozen tissue 9/6/2009 326

NVRL Procedure for Packaging Transport of Specimens for Influenza Virus 1. The specimen (swab container) to be sent should be wrapped in absorbent material (tissue paper or cotton wool which will act as absorbent material in event of a spillages) and placed in a secure secondary container (preferably plastic) 1. These containers may be purchased from Sarstedt 2. This container should be placed in a biohazard bag with the completed patient information form positioned in the special pouch section 3. The biohazard bag with the sample should be placed in a padded (jiffy bag)envelope 4. The envelope should be labelled with a hazard warning label, “Diagnostic Specimen” 5. The package should be addressed to: National Virus Reference Cylindrical protective containers meet all the requirements of the European standard EN 829 and the P Laboratory 650 packaging regulations for secondary packaging. University College Dublin All protective containers have absorbent linings. Belfield Dublin 4. 6. Please avoid use of staples for closure of packages, as these present a safety hazard to the laboratory staff 7. Please include the name and address of the sender to be contacted in case of damage or leakage to the package during transport 8. Specimens should reach the laboratory within 24 hours. Once taken and while awaiting transportation the specimen should be refrigerated at 4oC (but not frozen) 9. The specimen may be transported at room temperature, but it should not be kept unrefrigerated for more than 12 hours

NVRL Pandemic (H1N1) 2009 Influenza Laboratory Test Schedule During early Phases of Mitigation • Due to the high number of samples received for Influenza A(H1N1)v testing NRVL has revised their laboratory testing schedule which is outlined below: • Daily Laboratory testing of respiratory samples for Influenza A (H1N1)v • Samples need to arrive to the laboratory by 11am in order to be processed that day • The results for Influenza A (H1N1)v is 72 hours from receipt of the sample but are subjected to turnaround times due to specimen volume • In addition the 72 hour TAT may be exceeded in cases of weakly positive samples • Results will be issued to requesting clinicians within 96 hours of receipt of sample (Hard copy) • For patients with serious clinical manifestations http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/ weekend testing is available and can be accessed SwineInfluenza/AdviceforHealthProfessionals/L through the clinical team (087 9806448) aboratoryTesting/File,3875,en.pdf

NVRL Influenza Specimen Collection Kit • The National Virus Reference Laboratory provides these kits free of charge to GP’s participating in the Influenza Surveillance Programme • Influenza specimen collection kit containing the following: • Swabs • Transport media • Patient information forms • Plastic specimen bags • Pre – addressed sender labels • Plastic containers • Outer wrapper

NVRL Influenza Specimen Collection Protocol • GPs are required to provide a combined nose and throat swab specimen from cases presenting with suspected influenza or influenza like illness • The throat swab is used to abrade the tonsils and pharynx (see diagram) • The swab is then broken off into a bottle containing virus transport medium • The flexible wire nasal swab is inserted into the nostril and rubbed against and above the nasal turbinates • The swab is then agitated thoroughly into the same bottle as the throat swab to release virus-infected cells. The nasal swab may then be withdrawn and discarded safely Transport bottle • Ensure that the bottle lid is secured tightly onto the containing swab bottle to prevent leakages and virus transport • Label the bottle with Patient’s Name and Date of medium Birth • It is important to complete fully and legibly the patient information form provided

Packaging and Transportation to the NVRL Laboratory 1. Gp’s should be familiar with the regulations pertaining to conditions of posting for pathological specimens 2. The labelled primary container / specimen bottle should be placed in the plastic mailing container provided (1 specimen per container). – There should be sufficient absorbent wrapping to ensure that the specimen cannot move about the plastic container 3. The container should then be placed into a plastic biohazard bag with the completed patient information request form positioned in the special pouch section 4. The outer wrapper must be marked “Pathological Specimen-Fragile with Care” 5. It must also show the name and address of the sender to be contracted in case of damage or leaks 6. The package should be addressed to: National Virus Reference “Please avoid use of staples for closure of Laboratory packages, as these present a safety hazard University College Dublin to the laboratory staff.” Belfield Dublin 4. 7. Specimen should reach laboratory within 24 hours 8. If delays please store specimens at 4oC (but not frozen) nand sent to NVRL as soon as possible

Packaging and Transportation Step 1 Step2 Step 3 Labelled primary Plastic mailing container with Plastic specimen container containing primary specimen container bag containing specimen enclosed specimen and Step4 form Outer wrapper containing plastic specimen bag with specimen and form with specified labels

Pandemic (H1N1) 2009 Influenza Who Submission of Specimens • All samples from “highly suspicious cases” must be promptly referred to NVRL for investigation, as per agreed procedures • Any influenza strains detected should be provisionally characterised at the NVRL urgently and referred with available phylogenetic data urgently to the WHO Collaborating Centre in London for confirmation and sub typing (occasionally occurs) • Dr A. Hay • WHO Collaborating Centre for Reference and Research on Influenza • National Institute for Medical Research • Mill Hill, London NW7 1AA, United Kingdom • Fax: +44 208 906 44 77 • Email: whocc@nimr.mrc.ac.uk • http://www.nimr.mrc.ac.uk/wic/ 9/6/2009 333

NRVL Testing for Pandemic (H1N1) 2009 Influenza • 1. Health and Safety regulations on biological hazards (Safety, Health and Welfare at Work Act 2005 (No. 10 of 2005) • 2. European Agreement concerning the International Carriage of Dangerous Goods by road (ADR) Regulations (2007 edition) • 3. S.I. No 29 of 2004 - Carriage of Dangerous Goods by Road Regulations, 2004 • Biosafety: “Directive 90/679/EEC in S.I. No. 248/1998 — Safety, Health and Welfare At Work (Biological Agents) (Amendment) Regulations, 1998.” 9/6/2009 334

Pandemic (H1N1) 2009 Virus International Shipment Protocol As with all clinical specimens, respiratory specimens should be packaged and transported to the virology laboratory in accordance with national and international guidelines. Contact the National Virus Reference Laboratory or local laboratory for advice if concerned! 9/6/2009 335

Pandemic (H1N1) 2009 Virus Who Shipment Protocol Adapted from WHO E-tool-Intro Shipping requirements for Pandemic Influenza A(H1N1) 09 Virus specimens are described under: http://www.who.int/csr/resources/publications/swineflu/in structions-shipments/en/index.html All Shippers Must take the E-tool-intro coarse to be able to ship Infectious Substances “Category A” 9/6/2009 336

Pandemic (H1N1) 2009 Virus Who Shipment Protocol • If the shipment also includes other dangerous goods (such as liquid nitrogen or dry ice), shippers must be trained appropriately in the transport of those goods • Additional information can be found in the WHO document “Guidance on regulations for the transport of infectious substances”, available at: • http://www.who.int/csr/resources/publications/ biosafety/WHO_HSE_EPR_2008_10/en/index.ht ml 9/6/2009 337

Pandemic (H1N1) 2009 Virus Who Submission of Specimens • Shippers should note: • Specimens collected directly from humans or animals that are suspected or confirmed to be infected with the Pandemic Influenza A(H1N1) 09 Virus , including specimens from the respiratory tract (swabs) and blood specimens, should be shipped as: • "BIOLOGICAL SUBSTANCE, CATEGORY B" and assigned to UN 3373 • Pandemic Influenza A(H1N1) 09 Virus cultures (i.e. virus isolates) must be shipped as: • Category A "INFECTIOUS SUBSTANCE; AFFECTING HUMANS" and assigned to UN 2814 9/6/2009 338

Pandemic (H1N1) 2009 Virus Who Shipment of Specimens • Category A , Category B, Or Exempt • Packaging Samples • All samples must be packaged using triple packaging. • Triple packaging provides three layers of containment to protect the substances being shipped • These layers are primary, secondary, and outer containers. • The following diagram shows the basic concept of triple packages Must be packaged using triple packaging 9/6/2009 339

This Packaging is Used For Category A Infectious Substances 9/6/2009 340

Category A: Markings and Labels MARKINGS • All shippers must properly mark and label Category A packages. The following is a list of markings and labels for Category A packages: Markings • Shipper’s name, address, and telephone number u 4G/CLASS 6.2/02 • Receiver’s name, address, and telephone number n F/BVT 312103 • Name and telephone number of responsible person (who is available 24 hours a day until shipment arrives) INFECTIOUS SUBSTANCE, AFFECTING HUMANS • UN Specification Marking UN2814 • Proper Shipping Name and UN Number LABELS Labels • Infectious substance label • Package orientation label (only used when primary container exceeds 50ml) 9/6/2009 341

Pandemic (H1N1) 2009 Virus Category A Packing Requirements • Primary container is leakproof • Secondary container is leakproof • Outer container is rigid Triple Packaging Example • Pressure tested at 95kPa • Drop tested from 9m • Puncture tested at 7kg • UN specification marking • Shipper must be trained 9/6/2009 342

Steps For Packaging Category A Samples Swine influenza A(H1N1) 1. Open secondary container. virus cultures (i.e. virus isolates ) must be shipped 2. Insert absorbent material. as: 3. Don gloves. Category A "INFECTIOUS SUBSTANCE; AFFECTING 4. Cushion primary container. HUMANS" and assigned to UN 2814. 5. Place primary container in secondary container. Needs 6. Doff gloves. Dangerous Goods Declaration 7. Close secondary container. 8. Place secondary container in outer container. 9. Insert laboratory test instructions and description of materials. 10.Close outer container. 9/6/2009 343

Dangerous Goods Declaration • All shipments of Category A pathogens require a properly completed Dangerous Goods Declaration. This declaration must be signed by the shipper and serves as a legal contract between the shipper and operator • Samples classified as Category B or Exempt do not require this form Completed Form 9/6/2009 344

Air Waybill • All goods being shipped by air must have a completed Air Waybill 9/6/2009 345

This Packaging is Used For Category B Infectious Substances 9/6/2009 346

Category B Packaging Requirements • Primary container is leakproof • Secondary container is leakproof • Outer container: Either secondary or outer container is rigid – If the shipment is transported by air, the outer container must be rigid • Pressure tested at 95kPa • Drop tested from 1.2m 9/6/2009 347

Category B: Markings and Labels • All shippers must properly mark and label MARKINGS Category B packages. The following is a list of markings and labels for Category B packages: Markings • Shipper’s name, address, and telephone number UN 3373 BIOLOGICAL SUBSTANCE, CATEGORY B • Receiver’s name, address, and telephone number • UN Number • Proper Shipping Name Labels • None are required (unless shipping with dry ice) 9/6/2009 348

Steps For Packaging Category B Sample Specimens collected directly 1. Open secondary container. from humans or animals that are suspected or confirmed to 2. Insert absorbent material. be infected with the swine influenza A(H1N1) virus, 3. Don gloves. including specimens from the respiratory tract (swabs) and 4. Cushion primary container. blood specimens, should be shipped as : 5. Place primary container in secondary container. "BIOLOGICAL 6. Doff gloves. SUBSTANCE, CATEGORY B" 7. Close secondary container. and assigned to UN 3373. 8. Place secondary container in outer container. Does Not Need Dangerous Goods 9. Insert laboratory test instructions and description of Declaration materials. 10. Close outer container. 9/6/2009 349

Exempt Packaging Requirements • Primary container is leakproof • Secondary container is leakproof • Outer packaging must be of adequate strength 9/6/2009 350

Exempt Packaging Requirements Primary container (leakproof) Secondary container (leakproof) Absorbent and cushioning material Outer packaging 9/6/2009 351

Exempt Marking Labels • All shippers must properly mark and label MARKINGS Exempt packages. The following is a list of markings and labels for Exempt packages: • Markings • Shipper’s name, address, and telephone number EXEMPT HUMAN SPECIMEN • Receiver’s name, address, and telephone number • Proper Shipping Name EXEMPT ANIMAL SPECIMEN Labels • None are required (unless shipping with dry ice) 9/6/2009 352

Steps For Packaging Exempt Sample 1. Open secondary container. 2. Insert absorbent material. 3. Cushion primary container. 4. Place primary container in secondary container. 5. Close secondary container. 6. Place secondary container in outer container. 7. Insert laboratory test instructions and description of materials. 8. Close outer container. 9/6/2009 353

Health Protection Agency (HPA) Cat B Packaging Poster 9/6/2009 354

Biosaftey : Spill Clean-up Procedure 1. Wear gloves and protecting clothing, including face and eye protection if indicated 2. Cover the spill with a cloth or paper towels to contain it 3. Pour an appropriate disinfectant over the cloth or paper towels and the immediately surrounding area (5% bleach solutions are generally appropriate, but for spills on aircraft, quaternary ammonium disinfectants should be used) 4. Apply the disinfectant concentrically beginning at the outer margin of the spill area, working towards the centre 5. After about 30 min, clear away the materials. If there is broken glass or other sharps are involved, use a dustpan or a piece of stiff cardboard to collect the materials and deposit them into a puncture-resistant container for disposal 6. Clean and disinfect the area of the spillage (if necessary, repeat steps 2–5) 7. Dispose of contaminated materials into a leak-proof, puncture- resistant waste disposal container 8. After successful disinfection, report the incident to the competent authority and inform them that the site has been 9/6/2009 355 decontaminated

Pandemic (H1N1) 2009 Virus Vaccine For Ireland In Ireland advance purchase agreements with two manufacturers for the procurement of 7.7 million doses of pandemic vaccine have been negotiated! 1. Baxter 2. Glaxo-Smith-Kline (GSK) 9/6/2009 356

Canadian Lab Working on Pandemic (H1N1) 2009 Virus Vaccine • No Vaccine available at this time! NML Winnipeg Warning: Fake vaccine in Manilla July ,30 ,2009 • Late on May 6, Canada's National Microbiology Laboratory first completed the sequencing of the virus, publishing the result to GenBank Influenza A H1N1 virus is seen in an image taken using an electron • microscope, at PHAC's National Samples from Mexico, Nova Scotia and Microbiology Laboratory. (Public Health Agency of Canada, National Ontario had the same sequence, ruling Microbiology Laboratory) out genetic explanations for the greater severity of the Mexican cases 9/6/2009 357

Pandemic (H1N1) 2009 Virus Vaccine Resource Update • HX: Have been available for over 50 years. Generally, they are trivalent, i.e. they contain three different, inactivated virus strains, either whole viruses or parts or subunits of them – Because the flu virus is changing its antigenic shape constantly (either in minor drifts or in major shifts), the composition of the flu vaccine needs to be adapted to these changes regularly • The monitoring of these changes is done by the Global Influenza Surveillance Network of the World Health Organization (WHO) – At the beginning of each year the WHO makes a recommendation for the strains to be included into the vaccine for the coming influenza season • The following recommendations were provided to the WHO Director-General: – Immunize their health-care workers as a first priority to protect the essential health infrastructure • SAGE suggested the following groups for consideration, noting that countries need to determine their order of priority based on country-specific conditions: – Pregnant women – Those aged above 6 months with one of several chronic medical conditions – Healthy young adults of 15 to 49 years of age – Healthy children – Healthy adults of 50 to 64 years of age – Healthy adults of 65 years of age and above http://www.who.int/csr/disease/swineflu/notes/h1 n1_vaccine_20090713/en/index.html 9/6/2009 358

Vaccine Technology Overview • Traditional Egg-based Process (last 50 years) • Cell Culture Process (1990’s) – Grown in eggs – Mammalian (Kidney) cell culture – Moderate specific to original strain (growth of epidemic – Vaccine are not grown on the tissue but in the single cells of viruses in eggs result in variants that are antigenically distinct the tissue from the original viruses – Highly specific to original strain (strains grown in cell cultures – Low Yield (approx 1-3 eggs per dose) equal the original clinical isolates) – Allergies to egg albumin? – High Yield – Potential impurities in eggs (antibiotics, other viruses) may – Virus grown in mammalian cell culture is therefore more cause sterility problems representative of the circulating wild type virus than that – Long Process (6-12 months) grown in eggs – A flu pandemic could probably not be contained and defeated – Cell culture based systems, however, could be rapidly on egg-based production, because the production takes too expanded and scaled up in times of emergency long and eggs don’t grow on demand – Up -front costs for operational readiness of such plants (with – Emerging endemic viruses sometimes do not grow at all in its huge fermenters) are much higher than the costs for egg – eggs based systems – Egg-based production of flu vaccines is well established and – Ie. Polio Vaccine cost-effective – Example: Pharmaceutical company - Novarits – Example: Pharmaceutical company- Glaxo-Smith-Kline (GSK) • Transient Expression of haemagulltinin – Insect cell culture – Very High Yield – Not very well established but is cost effective – Low production time 9/6/2009 359

Vaccine Development Classical Reassortment • The goal of reassortment is to combine the desired HA and NA antigens from the target strain (flu strain 1) with genes from a harmless strain that grows well in an egg (flu strain 2) • The illustration details the following steps in creating the vaccine: – Flu strains 1 and 2 are injected into a fertilized chicken egg – The genes from flu strain 1 multiply and mix with the genes from flu strain 2, forming as many as 256 possible gene combinations – Researchers search the many combinations for the flu strain that contains the HA and NA genes from flu strain 1 and remaining genes from flu strain 2 that ensures that it is able to grow efficiently in eggs. – This new reassortant flu strain and two other flu strains will make up next year’s vaccine. • This image is in the public domain. Please credit the National Institute of Allergy and Infectious Diseases (NIAID). 9/6/2009 360

Vaccine Development Reverse Genetics • Reverse Genetics • A flu virus contains eight gene segments. One of the gene segments codes for the surface antigen hemagglutinin (HA) and another codes for the surface antigen neuraminidase (NA) • Scientists can custom-make a flu strain by assembling genes that code for the desired features. Two genes representing the HA and NA antigens are selected from the target strain (flu strain 1), while the remaining six genes come from a virus that's time-tested for its ability to grow inside an egg (flu strain 2). (Although the influenza virus actually uses RNA as its genetic material, the researchers make complementary pieces of DNA because DNA is easier to work with.) • The illustration details the following steps in creating the vaccine: – After removing the dangerous part of the HA gene, scientists splice the HA and NA genes from flu strain 1 into circular pieces of DNA called plasmids. – Additional plasmids are created using the remaining six genes found in flu strain 2. – Scientists insert the HA and NA plasmids from flu strain 1 and the six plasmids carrying genes from flu strain 2 into animal cells growing in the laboratory. – The genes in the plasmids instruct the animal cells to make the desired new flu strain • This image is in the public domain. Please credit the National Institute of Allergy and Infectious Diseases (NIAID). 9/6/2009 361

Pandemic (H1N1) 2009 Virus Vaccine Development Process Seasonal 1. Collection of specimens and disease/epidemiology data (All year round) A(H1N1) 09 2. Diagnosis and virus isolation ,preliminary analysis (Hrs to 3 wks) 2a. Virus Isolation in eggs Vaccine (1-3 wks) development 3. Ferret antisera production Approx 6 -10 (3-5 weeks) months 4. Thorough antigenic and genetic analysis (1-3 wks) 4a. Serological Studies (3-16 wks) 5.Review and selection of candidate viruses for vaccine use (1-3 wks) Repeat process Repeat process 6a. Classical Reassortment of 6b. Reassortment of high high growth viruses growth using reverse genetics (3-4wks) and full safety testing (8 wks) 7a. Antigenic and genetic 9a. Development of 9b. Development of 7b. Antigenic and genetic characterizations of 8. Evaluation of growth standardized reagents standardized reagents characterizations of reassortments property fir inactivated vaccines for inactivated ressortment (3 wks) (4wks) (6wks) vaccines (3 wks) (4wks) 9/6/2009 Availability of vaccine virus and standardised reagents Adapted from WHO H5N1 vaccine development

Pandemic (H1N1) 2009 Virus Vaccine Development Process Glossary • Novel (new) subtype of human influenza A virus. This term refers to human influenza viruses that have haemagglutinin and neuraminidase antigens that are distinct from seasonal influenza viruses and have the potential to cause a pandemic. • Clinical specimens (original). These are materials collected from humans, generally in order to confirm a diagnosis. For influenza, most commonly, clinical specimens are taken from the respiratory tract (for example, swabs and aspirated fluid) but they can be from other locations. Clinical specimens can be frozen and stored for later use • Influenza reference viruses. These are wild-type influenza viruses that WHO has selected as representative of important groups of influenza viruses on the basis of extensive antigenic and genetic studies and comparisons with viruses from many countries. As the influenza viruses evolve in nature, new reference viruses are selected. • Wild-type influenza viruses (synonym: virus isolates). These are influenza viruses that have been cultured either in eggs or cells (i.e. isolated) directly from clinical specimens and have not been modified. • “Classical” reassortment. This is a non-patented laboratory technique that is often used to make (seasonal) candidate vaccine viruses • Genetic reassortment. In this process genes from two or more influenza viruses are mixed in different combinations, resulting in hybrid viruses with genetic characteristics of each parent virus. This process occurs in nature but can also be done in a laboratory using “classical” reassortment or reverse genetics • High-growth reassortant viruses. These are influenza viruses that have been genetically modified to grow better in eggs for optimal vaccine production. • Reverse genetics. This is a laboratory technique that is used to construct or modify influenza viruses and is protected by patents in several countries. It is used to render highly pathogenic H5N1 viruses less dangerous. • Reagents for influenza vaccine standardization. These reagents are used to standardize the amount of haemagglutinin protein in influenza vaccines as required by regulatory agencies. The reagents have to be produced in large quantities so that all vaccine batches can be tested. • Seed viruses. These are influenza viruses prepared from candidate influenza vaccine viruses by individual manufacturers for the manufacturer’s specific vaccine-production process. 9/6/2009 363

Results of Haemagglutination Inhibition Tests of Pandemic Influenza A(H1N1) 2009 Viruses With Post‐infection Ferret SeraA 9/6/2009 364

Viral Gene Sequences to Assist Update Diagnostics for Pandemic Influenza A(H1N1) 09 Virus - GenBank Accession Numbers Pandemic Influenza A(H1N1) 09 Virus The WHO Collaborating Centre for influenza in CDC Quadruple Reassortant Lineage Atlanta USA has posted the full genome sequences of swine influenza (North American and Eurasian A/California/04/2009 (H1N1) influenza virus on the Swine/Avian/Human) GenBank sequence database. To access, go to: http://www.ncbi.nlm.nih.gov/sites/entrez?db=nuccore PB2 &itool=toolbar, then enter the accession number as shown below: PB1 • PB2 gene accession number is: FJ966079 PA • PB1 gene accession number is: FJ966080 HA • PA gene accession number is: FJ966081 NP • HA gene accession number is: FJ966082 • NP gene accession number is: FJ966083 NA • NA gene accession number is: FJ966084 M •M gene accession number is: FJ966085 NS • NS gene accession number is: FJ966086 Tip: to access all the gene sequence records at once, copy the following line of text and paste Classical swine, North American Lineage it into the search bar in the above GenBank web link. FJ966079,FJ966080,FJ966081,FJ966082,FJ966083,FJ9660 Avian, North American Lineage 84,FJ966085,FJ966086 Seasonal H3N2 Eurasian swine Lineage 9/6/2009 365

Pandemic (H1N1) 2009 Virus Gene sequences of the currently available reassortant candidate vaccine viruses: • X-179A – The accession numbers of the HA and NA gene sequences of X-179A in GenBank is: • HA: GQ214335 • http://www.ncbi.nlm.nih.gov/nuccore/238623303 • NA: GQ214336 • http://www.ncbi.nlm.nih.gov/nuccore/238623305 • IDCDC-RG15 – The accession numbers of the HA and NA gene sequences of IDCDC-RG15 in GenBank is: • HA: GQ219781 • http://www.ncbi.nlm.nih.gov/nuccore/238623307 • NA: GQ219782 • http://www.ncbi.nlm.nih.gov/nuccore/238623309 • IVR-153 – The accession numbers of the HA and NA gene sequences of IVR-153 in GISAID is: • HA: EPI181843 • http://platform.gisaid.org/dante-cms/live/struktur.jdante?aid=1131 • NA: EPI181844 • http://platform.gisaid.org/dante-cms/live/struktur.jdante?aid=1131 9/6/2009 366

Pandemic (H1N1) 2009 Virus International Vaccine Candidates • Wild type influenza virus: • Traditional reassortant viruses are derived only from wild type viruses isolated and grown in hens’ eggs, or in a validated clean cell culture system. • A/California/7/2009 (egg isolate) – classical reassortment and reverse genetics • A/England/195/2009 (MDCK cell isolate) – reverse genetics • A/California/4/2009 (MDCK isolate) – reverse genetics • A/Texas/5/2009 (MDCK isolate) - reverse genetics • A/Ohio/7/2009 (MDCK isolate) - reverse genetics • A/New York/20/2009 (MDCK isolate) - reverse genetics 9/6/2009 367

) Pandemic (H1N1) 2009Vaccine Virus Development Summary Candidate vaccine viruses using reverse Candidate vaccine viruses using classical Development of vaccine potency reagents Wild type viruses have been/ are being sent genetics technology are being developed by: reassortment technology are being for inactivated vaccines against Influenza to vaccine manufacturers on request developed by: A(H1N1) is planned in: including: Centers for Disease Control and Prevention NIBSC, UK, from NIBSC, UK Baxter (CDC), Atlanta USA A/California/7/2009(H1N1)swl, an egg virus enquiries@nibsc.ac.uk August 8 2009 Baxter International says it has rdonis@cdc.gov isolate produced its first commercial batches of a swine flu enquiries@nibsc.ac.uk vaccine called Celvapan A/H1N1. National Institute for Biological Standards New York Medical College, USA, from CBER FDA, USA CSL Limited and Control (NIBSC) A/California/7/2009(H1N1)swl zhiping.ye@fda.hhs.gov 20 July 2009 human trials of swine flu vaccine enquiries@nibsc.ac.uk zhiping.ye@fda.hhs.gov begin in Australia Centre for Biologics Evaluation and Research CSL Limited, Australia, from Therapeutic Goods Administration GlaxoSmithKline Biologicals (CBER) A/California/7/2009(H1N1)swl gary.grohmann@health.gov.au donating 50 million doses to the WHO. zhiping.ye@fda.hhs.gov gary.grohmann@health.gov.au St. Jude Children’s Research ERL NIID, Japan MedImmune Hospital,Memphis USA mtashiro@nih.go.jp richard.webby@stjude.org National Institute of Infectious Diseases Microgen (NIID), Japan mtashiro@nih.go.jp Nobilon International Novartis June 15 2007 cell cultured vaccine ready for first stage Omninvest Vaccines Sanofi Pasteur June 17 2009 Donates 10,000,000 vaccine doses to WHO July 26 2009 vaccine is being tested in a yearlong trial of 6,000 people of all ages in Britain, Germany Adapted from WHO vaccine policy May 18 2009 and the United States 9/6/2009 368

Pandemic (H1N1) 2009 Virus International Vaccine Candidates Candidate influenza Parental H1N1 virus Laboratory vaccine viruses NYMCX-179A conventional A/California/7/2009 NYMC, USA reassortant virus IVR-153 conventional A/California/7/2009 CSL, Australia reassortant virus IDCDC –RG15 reverse A/Texas/5/2009 CDC, USA genetics virus CBER-RG2 reverse genetics A/California/04/2009 CBER, USA virus NIBRG-121 reverse A/California/7/2009 NIBSC, UK genetics virus 9/6/2009 369

Pandemic (H1N1) 2009 Virus NIBSC Candidate Vaccine Viruses Candidate Parental H1N1 NIBSC code Availability influenza vaccine virus viruses NIBRG-121 A/California/7/2009 09/122 Now 27/05/09 NYMCX-179A A/California/7/2009 09/124 Now W/C 8/06/09 IVR-153 A/California/7/2009 09/144 Now Previously VI 1525 2/06/09 9/6/2009 370

Reagents for Single Radial Diffusion Assay of Influenza A (H1N1)v Virus Vaccine Reagents for NIBSC code Availability influenza Vaccine Standardisation A/California/7/2009 NA Now antigen (cell derived) A/California/7/2009 NA Now antigen (egg derived) A/California/7/2009 09/142 Now antiserum 9/6/2009 371

Influenza A (H1N1)v Vaccine Development: NIBRG‐121 27 May 2009 • NIBRG‐121 (NIBRG‐121 reassortant virus) • A candidate reassortant vaccine virus (NIBRG‐121) has been developed, using reverse genetics technology, from an A/California/7/2009(H1N1)v virus, by the National Institute for Biological Standards and Control (NIBSC), Potters Bar, Hertfordshire, United Kingdom. • The haemagglutinin (HA) and neuraminidase (NA) sequences of the A/California/7/2009(H1N1)v virus can be found on the public web site of GenBank via the following links: • HA sequence – http://www.ncbi.nlm.nih.gov/nuccore/227977171?ordinalpos=1&itool=Ent rezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSu m • NA sequence – http://www.ncbi.nlm.nih.gov/nuccore/229396468?ordinalpos=1&itool=Ent rezSystem2.PEntrez.Sequence.Sequence_ResultsPanel.Sequence_RVDocSu m 9/6/2009 372

Pandemic (H1N1) 2009 Virus NIBRG‐121 (NIBRG‐121 Reassortant Virus) • Now Available from: • Division of Virology • National Institute for Biological Standards and Control • Blanche Lane, South Mimms, Potters Bar • Hertfordshire, EN6 3QG, United Kingdom • E‐mail: enquiries@nibsc.hpa.org.u • k or standards@nibsc.hpa.org.uk • http://www.nibsc.ac.uk/flu_site/viruses_reagents.html • The candidate reassortant vaccine virus contains infectious materials and should be handled only in appropriate containment facilities (until completion of the above‐mentioned safety tests, it is recommended to use biosafety level 2 plus *BSL‐2 plus+ facilities with biosafety level 3 *BSL‐3+ practices)3 9/6/2009 373

Irelands Seasonal Influenza Vaccine Composition 2009-10 • World Health Organization (WHO) 2009-2010 • World Health Organization (WHO) 2009 and EMEA/CHMP/BWP/ 23 April 2009 • Southern Hemisphere: • Northern Hemisphere: Seasonal Influenza Vaccine Composition Seasonal Influenza Vaccine Composition • Trivalent vaccine containing: • Trivalent vaccine containing: – A (H1N1): an A/Brisbane/59/2007 (H1N1) - – A/Brisbane/59/2007 (H1N1)-like strain like strain, – an A/ Brisbane/10/2007 (H3N2)-like strain – A (H3N2): an A/Brisbane/10/2007 (H3N2) - – a B/ Brisbane/60/2008-like strain like strain, – B: a B/Florida/4/2006 - like strain Map: International Co-circulation of 2009 H1N1 and Seasonal Influenza http://www.who.int/csr/ don/Virologicaldata2009 _08_28.pdf Week 34-35 is the beginning of Flu Season Week 34 -35 is the end Of Flu Season The Pandemic (H1N1) vaccine trials will test the vaccine's safety and whether one or two injections are necessary. Update: The vaccines will be given in two injections 3-4 weeks apart! 9/6/2009 Seasonal in one arm and the Pandemic Vaccine in the other! 374 Get your Flu Shot!

Pandemic (H1N1) 2009 Virus Irish Vaccine Timeline in Context to EpiCurve Vaccine campaign begins In early Overall cases and health October/November impact diminishes 2 1. Vaccine development process 2. Vaccine campaign begins! Vaccine development 3 3. Overall cases and health impact process begins in April diminishes Daily Cases 1 Pandemic Outbreak with Vaccine Intervention April May June July Aug Sept Oct Nov Dec Jan Feb March April May June July Aug 2009 2010 The early use of pandemic (H1N1) vaccine + community mitigation strategies will diminish the overall impact of the pandemic especially in the high risk categories and antivirals will provide more time for low risk groups to obtain vaccine 9/6/2009 375

Performance Improvement for Irish Vaccination Targets Guidance on Allocating Use of specific pandemic and Targeting Pandemic influenza vaccines during the H1N1 Influenza Vaccine 2009 pandemic 9/6/2009 377

Vaccination Tiers and Targets Performance Improvement Summary • Dissemination of the Novel Influenza Vaccine is imperative and tiers and targets is an Great Resource for Clinicians excellent example of the possible breakdown or needs assessment of high risk groups! • Incorporating the Empirical Model (HPA Model) and Pandemic Severity Index with also interrelating tiers and targets Irelands pandemic groups and committees have the potential to target vaccination groups effectively and assess future needs when the Influenza A(H1N1) vaccine becomes available in the Autumn! • Allocation of funds for the vaccine for Irelands population should be based upon a needs assessment and not only on general assumptions of clinical attack rates in the HPA model! • Cost-effective planning is essential during the economic times! • ? How much vaccine do you really need to pre-order keeping pandemic severity in mind? • Ireland Pre ordered 7.7 million Pandemic (H1N1) vaccine dosages! • 2nd wave could mutate with resistance! Multi-dosages/Difficult to find the balance! • Proactive better than reactive! Finding the balance Pandemic Severity Pandemic Influenza Preparedness for Ireland: Population Vaccine Advice of the Pandemic Influenza Expert Group; Chapter 6 Public Health Response: Vaccines First Vaccine Vial from Novartis 9/6/2009 378

WHO “SAGE” Recommendations For Vaccine Distribution July, 7, 2009 • The following recommendations were provided to the WHO Director-General: A. All countries should immunize their health-care workers as a first priority to protect the essential health infrastructure ! – As vaccines available initially will not be sufficient, a step-wise approach to vaccinate particular groups may be considered. B. SAGE suggested the following groups for consideration, noting that countries need to determine their order of priority based on country-specific conditions: 1. Pregnant women 2. Those aged above 6 months with one of several chronic medical conditions 3. Healthy young adults of 15 to 49 years of age 4. Healthy children 5. Healthy adults of 50 to 64 years of age 6. Healthy adults of 65 years of age and above http://www.who.int/csr/diseas e/swineflu/notes/h1n1_vaccine 9/6/2009 _20090713/en/index.html 379

Pandemic (H1N1) 2009 Virus Vaccine Campaign Ireland • According to HSE's national director of population health Dr Pat Doorley that planning the vaccination programme was a serious logistical exercise as everyone will be offered two doses of the vaccine, which will have to be taken three or four weeks apart. • “We have to look at establishing clinics, the scheduling of appointments, how we identify at-risk groups, uptake, and recording of the vaccinations.” • Sept 3 2009 Dr Pat Doorley mentions 30,000 doses of the swine flu vaccine have already arrived in the State but the HSE expects it will be at least mid October before it will be able to begin the vaccination programme 1. Health care workers and high risk groups would be offered the H1N1 pandemic vaccine 2. All children would then be offered the vaccine in schools 3. General public would be offered it at around 60 special vaccination clinics which would be set up National Immunisation Website www.immunisation.ie 9/6/2009 380

Mass Prophylaxis Staffing Model Bioterrorism and Epidemic Outbreak Response Model (BERM) • THE WEILL/CORNELL BIOTERRORISM AND EPIDEMIC OUTBREAK RESPONSE MODEL : (BERM) A MASS PROPHYLAXIS PLANNING TOOL VER 2.0 – (originally used for smallpox planning but can be adapted to Pandemic(H1N1) 2009 Virus • Download Excel File • This tool may be downloaded from this Web page as a Microsoft® Excel workbook. To download the file, right click on the link and then select "Save Target As" (Internet Explorer) or "Save Link As" (Firefox™, Netscape®): 9/6/2009 381

Pandemic(H1N1) 2009 Virus Antiviral Medications Oseltamivir and Relenza is not a substitute for the influenza vaccine! 9/6/2009 382

Management of Pandemic (H1N1) 2009 Virus During the Treatment Phase • WHO Phase 6- HPSC- Mitigation (Stage 2) “Treatment Phase” • Update July ,29, 2009 – Patient has severe symptoms – Patient is in a Defined Risk Group Defined risk groups are: Chronic respiratory, heart, kidney, liver, neurological disease; immunosuppression (whether caused by disease or treatment); diabetes mellitus; people aged 65 years and older; children <5 (children <2 are at particular risk of influenza); people on medication for asthma, bariatric people (BMI ≥40) and pregnant women • Chemoprophylaxis is no longer generally recommended for contacts – Physicians may exercise judgement in individual cases for chemoprophylaxis – Possible scenarios include: • Nursing homes • Educational residential centres (Consult DPH) 9/6/2009 383 A flu clinic in Birmingham, England!

Groups at High Risk for Complications From Pandemic (H1N1) 2009 Virus • High Risk groups include: • Chronic liver disease – Cirrhosis • Age – Inflammatory bowel disease – Persons aged 65 years or older • Chronic metabolic disorders – Infants aged 12–24 months; Children <5 (children <2 – Diabetes mellitus requiring insulin or oral are at particular risk of influenza) hypoglycaemic drugs • Pregnancy – Sickle cell anaemia and other haemoglobinopathies – Especially during third trimester and four weeks post- • Immunosuppression and malignancy due to partum disease or treatment • Bariatric – Asplenia or splenic dysfunction – BMI ≥40 – HIV infection at all stages • Chronic respiratory disease – Malignancy – Asthma requiring continuous or repeated use of – Patients undergoing chemotherapy or transplant inhaled or systemic steroids or with previous leading to immunosuppression exacerbations requiring hospital admission – Individuals on or likely to be on systemic steroids for – Children who have previously been admitted to more than a month at a dose equivalent to hospital with lower respiratory tract disease prednisolone at 20mg or more per day (any age) or for – Such as cystic fibrosis in children or chronic obstructive children under 20kg a dose of 1mg per kg per day pulmonary disease in adults – Diseases that requiring long-term aspirin therapy • Chronic heart disease rheumatoid arthritis or Kawasaki disease – Hemodynamically significant cardiac disease • Chronic neurological disease – Congenital heart disease – Neuromuscular disorders – Hypertension with cardiac complications – Seizure disorders – Chronic heart failure – Cognitive dysfunction that may compromise the – Individuals requiring regular medication and/or follow handling of respiratory secretions up for ischaemic heart disease • Chronic renal disease Not an inclusive list! 384 9/6/2009

Pandemic (H1N1) 2009 Virus Antivirals “Pregnant Women” • Oseltamivir, zanamivir, amantadine, and rimantadine are all “Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women • EU: Following a review of the available data for Tamiflu and Relenza, the CHMP concluded that the benefits of using these medicines in pregnant or breastfeeding women outweigh the risks in case of an Pandemic Influenza A(H1N1) 09 Virus pandemic • At present, the groups identified at higher risk of influenza- related complications from seasonal influenza and the H1N1 2009 include pregnant women in their second and especially the third trimester and women within four weeks post- partum. • Experience with past pandemics demonstrates they can be affected disproportionately compared to non-pregnant women • Currently, little is known about whether influenza viruses are transmitted to the foetus through the placenta, although this class of viruses is not considered to be teratogenic in humans 9/6/2009 385

Treatment With Antivirals In Pregnancy Summary • Update as of July 28 2009 from The Pandemic Tamiflu dosage regime Influenza Expert Group advice is that: July, 31, 2009 • “Chemoprophylaxis is no longer routinely recommended in pregnancy – Pregnant women with severe symptoms in the first trimester should receive oseltamivir (Tamiflu) – Oseltamivir (Tamiflu) should be considered for pregnant women with mild symptoms in the first trimester if they have other co‐morbidities – Pregnant women with mild symptoms of influenza like illness and no co‐morbidities in the first trimester should be observed and oseltamivir (Tamiflu) withheld unless clinically indicated – Pregnant women with influenza like illness in the second and third trimesters should receive oseltamivir (Tamiflu)” http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenz a/SwineInfluenza/AdviceforHealthProfessional • Available for download at HPSC! s/AntiviralMedicines/File,3857,en.pdf 9/6/2009 386

Treatment With Antivirals In Pregnancy (PIEG) • As of the 3rd ,September 2009 Pandemic Influenza Expert Group (PIEG) has produced new overview/advice for antiviral use in pregnancy and infection prevention and control for obstetrical units Pages 1-9 Pages 1-4 http://www.hpsc.ie/hpsc/A- http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflue Z/EmergencyPlanning/AvianPandemicInfl nza/SwineInfluenza/AdviceforHealthProfessi uenza/SwineInfluenza/AdviceforHealthPr onals/Pregnancy/File,3944,en.pdf ofessionals/Pregnancy/File,3945,en.pdf 9/6/2009 387

Pandemic (H1N1) 2009 Virus Special Considerations for Children • Aspirin or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) should not be administered to any confirmed or suspected ill case of Pandemic Influenza A(H1N1) 09 Virus infection aged 18 years old and younger due to the risk of Reye syndrome • For relief of fever, other anti-pyretic medications are recommended such as acetaminophen or non steroidal anti- inflammatory drugs • Long term aspirin use in children >14 years old are considered in the high risk category for antivirals 9/6/2009 388

Pandemic (H1N1) 2009 Virus Antiviral Medications 2 Classes of Medications Available • M2 Inhibitors :Adamantanes – Amantadine, Rimantadine – Activity only against influenza A viruses • Neuraminidase inhibitors – Oseltamivir, Zanamivir. (Primivir experimental) – Activity against influenza A and B viruses Class Effective Against Drug Name (INN) Brand Name Year Approved Manufacturer M2 inhibitors Influenza A Amantadine Symmetrel 1976 Endo (adamantane Pharmaceuticals derivatives Rimantadine Flumadine 1994 Forest Laboratories Neuraminidase Influenza A & B Zanamivir Relenza 1999 GlaxoSmithKline inhibitors Hoffmann-La Oseltamivir Tamiflu 1999 Rochene 9/6/2009 389

Pandemic (H1N1) 2009 Virus Antivirals Oseltamivir, Zanamivir • Chemically related • Different routes of administration – Oseltamivir (Tamiflu): Tablet, suspension – Zanamivir (Relenza): Orally inhaled powder • Mechanism of action: – Block active site of neuraminidase – Reduce the amount of viral particles released from infected cells • Decrease shedding of influenza A and influenza B viruses 9/6/2009 390

Blocks receptor sites Blocks receptor sites 9/6/2009 391

9/6/2009 392

9/6/2009 393

Pandemic (H1N1) 2009 Virus Antiviral Purpose in Pandemics 1. Delay the Outbreak 1 2. Decompress peak burden on hospital infrastructure 3. Diminish overall cases and No intervention health impacts 2 Daily Cases Pandemic Outbreak with Intervention 3 Days Since first case The early use of antivirals + community mitigation strategies could delay the 9/6/2009 pandemic, giving time to develop a targeted pandemic vaccine 394

Pandemic (H1N1) 2009 Virus Antiviral Treatment • Only 2 antiviral medications are equally efficacious when used for early treatment – Decrease the duration and symptoms of uncomplicated influenza by approximately 1 day – Decrease viral shedding • Early treatment with neuraminidase inhibitors can reduce some complications – Otitis media, lower respiratory tract complications, antibiotic use, hospitalizations 9/6/2009 395

Pandemic Influenza Expert Group (PIEG) On Antivirals • According to the Pandemic Influenza Expert Group (PIEG) • Treatment with NAI (within 48 hours) for seasonal influenza leads to reduction of: • 0.4 -1 days in duration of symptoms • 25-43% of complications requiring antibiotics • 55% in Lower Respiratory Tract Infections • 34% in need for antibiotics • 59% in hospitalisations • 44% in otitis in children 9/6/2009 396

Pandemic (H1N1) 2009 Virus Neuraminidase Inhibitor Resistance • Cross-resistance • Frequency – 5.5% in oseltamivir pediatric treatment study (U.S.) – 18% in oseltamivir pediatric The Strategy for the treatment study (Japan) Control of Antimicrobial • Global Neuraminidase Inhibitor Susceptibility Resistance in Ireland Network • HPSC “Antiviral drugs are a valuable resource and need to be used judiciously so as to avoid the development of resistance and to ensure that those who need them can avail of them.” 9/6/2009 397

Pandemic (H1N1) 2009 Virus Antivirals Great Resource for Clinicians • Director Schuchat said that the virus was resistant to Amantadine and Rimantadine • Susceptible to Oseltamivir (Tamiflu) and Zanamivir (Relenza) http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/Guidance/Pandemi cInfluenzaPreparednessforIreland/File,3257,en.pdf 9/6/2009 398

Pandemic (H1N1) 2009 Virus Antiviral Resistance • ECDC: Antiviral resistance detected in influenza viruses from European countries during the season 2008/2009, by virus subtype and drug class (updated 12/06/2009) US : Week 33 US: During week 34 (August 23-29, 2009), The majority of 2009 influenza A (H1N1) viruses are susceptible to the neuraminidase inhibitor antiviral medication oseltamivir, however rare sporadic cases of oseltamivir resistant 2009 influenza A (H1N1) viruses have been detected worldwide, including 9 9/6/2009 viruses in the United States 399

Pandemic (H1N1) 2009 Virus Antiviral Resistance • HX of neuraminidase segment gene (position 274 in N2 numbering system) – This mutation has been described in the past, associated with so-called secondary resistance to oseltamivir acquired during treatment of both A(H1N1)v and A(H5N1) virus infections • Worldwide sporadic identification of 18 persons with oseltamivir-resistant Pandemic (H1N1) 2009 Virus infection; all viruses had the same mutation that confers resistance, H274Y (H275Y in N2 numbering), in the neuraminidase protein (Japan (4), USA (9), China, Hong Kong SAR China (2), and 1 in Denmark, Canada, Singapore) On June 29, 2009, the National Influenza Center in Denmark reported an oseltamivir-resistant novel influenza A On July 21, 2009 Canada reported its first (H1N1) virus from an unknown date. The On July 3, The Hong Kong Department of Health case of oseltamivir resistant pandemic virus was isolated from a patient who reported a resistant virus isolated from a 16 year- influenza A (H1N1)v. The strain was became ill while taking a old girl who had a fever upon arrival at the Hong isolated from a 59 year old male from chemoprophylaxis dose of oseltamivir to Kong International airport on June 11, 2009. Her Quebec with underlying medical prevent influenza infection after exposure symptoms began prior to boarding the plane in conditions who received post-exposure to an ill person. San Francisco, California. The patient had not prophylaxis following illness in a family taken antiviral agents and reported no illness member (the man's son). The isolate had among close contacts. a mutation at the H274Y location. On Aug 7 2009 China confirms resistance of a 63 year old female with an oseltamivir- 1 1 resistant novel influenza A (H1N1) 2 2 7 4 On July 2, 2009, a person infected with an On Aug 28 2009 CDC confirms 7 reports of oseltamivir oseltamivir-resistant novel influenza A resistant to pandemic influenza A (H1N1)v (H1N1) virus was reported from Japan from ( 2 in Immunosuppressed patients) 1 an illness on May 15, 2009. This patient also The 2 isolates had a mutation at the H275Y location became ill while receiving oseltamivir for indicating oseltamivir resistance. chemoprophylaxis. Aug 18 2009 Chile: WHO /OIE confirms reports of pandemic (H1N1) species jump to turkeys on 2 farms which no birds were culled but quarantined till symptoms resolve 9/6/2009 All mild resistance with no deaths - 2nd line Antiviral “Relenza “effective in treatment 400

Pandemic (H1N1) 2009 Virus Antiviral Resistance • Another important mutation that has been identified in some isolates from Shanghai is the E627K mutation in the PB2 gene This mutation renders the virus more fit to replicate at 33°C, the temperature of the human nose during winter months • The PB2 gene of the 2009 H1N1 virus is derived from an avian source and, accordingly, contains a genetic sequence optimizing replication at 41°C, the normal temperature of avian species Swine isolate • In conclusion: • The emergence of the E627K mutation and its potential for worldwide progression could foster more efficient spread of the virus, increasing the proportion of persons expected to become ill • July 5 2009: Southern hemisphere sees H3N2 seasonal flu variant: • Laboratory experts in the southern hemisphere are reporting the circulation of a drifted strain of the seasonal H3N2 influenza virus, raising the threat of a vaccine mismatch for the northern hemisphere's WHO update 63 Aug 28 2009 End of southern hemisphere flu Season (peak is decreasing in southeast and peak is still showing resilience in southwest ) and the northern hemisphere flu season is just beginning! upcoming flu season No change in virulence of Pandemic Influenza (H1N1)2009 strain! • WHO collaborating centres are investigating! 9/6/2009 401

GenBank Sequences From Pandemic (H1N1) 2009 Viruses Oseltamivir-resistant Pandemic Influenza A(H1N1) 09 Virus Infection Summary of first few cases Reference: RIKEN FAMSBASE

GenBank Sequences from Pandemic (H1N1) 2009 Viruses for Ireland • 18-JUN-2009 • National Virus Reference Laboratory, University College Dublin, Belfield, Dublin D4 • Organism : Influenza A virus (A/Dublin/03/2009(H1N1) [NA of A/Dublin/03/2009(H1N1) : GQ281077] • Collection date= 26-May-2009 Mutation information • Isolation source= Throat swab Multiple alignment against 107 NA sequences • Host = Homo sapiens; gender F; age 21 of swine influenza [H1N1] No Mutations or resistance in all specimens!

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, • Collection date= 09-Jun-2009 • Organism= Influenza A virus (A/Denmark/528/2009(H1N1) • Serotype = H1N1 • Isolation source = gender : Female; age:21y • Oseltamivir resistant, Zanamivir sensitive, Amantidine resistant (31N in M2)

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • 08-JUL-2009 • National Institute of Infectious Diseases Tokyo , Japan • Collection date= 09-Jun-2009 • Organism : Influenza A virus : A/Osaka/180/2009(H1N1) • Serotype = H1N1 • MDCK2: Resistance to oseltamivir • Influenza A virus (A/Osaka/180/2009(H1N1)) segment 6 neuraminidase (NA) gene, [NA of A/Osaka/180/2009(H1N1) : GQ365445] Mutation information Multiple alignment against 122 NA sequences of swine influenza [H1N1]

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • 21-JUL-2009 • National Institute of Infectious Diseases Tokyo , Japan • Collection date= 2009 • Organism = Influenza A virus (A/Yamaguchi/22/2009(H1N1) • Serotype = H1N1 • MDCK2: Resistance to oseltamivir • * This sequence has the H274Y mutation that might confer resistance to Oseltamivir.

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • 21-JUL-2009 • National Institute of Infectious Diseases Tokyo , Japan • Collection date= 2009 • Organism = Influenza A virus (A/Hong Kong/2369/2009(H1N1) • Serotype = H1N1 • Host = Homo sapiens • MDCK2: Resistance to oseltamivir • Influenza A virus (A/Hong Kong/2369/2009(H1N1)) segment 6 neuraminidase (NA) gene • [NA of A/Hong Kong/2369/2009(H1N1) : GQ351316] Mutation information Multiple alignment against 112 NA sequences of swine influenza [H1N1]

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • 07-AUG-2009 (submitted) • Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention • Collection date: 13-Jun-2009 • Organism = Influenza A virus (A/Hunan/SWL3/2009(H1N1) • Serotype = H1N1 • Host = Homo sapiens, gender F, age 63 * This sequence has the H274Y mutation that might confer resistance to Oseltamivir. 9/6/2009 408

GenBank Sequences from Pandemic (H1N1) 2009 Viruses • Submitted 21-AUG-2009 • WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., Atlanta, GA 30333,USA • Influenza A virus (A/Washington/28/2009(H1N1) • Serotype = H1N1 • Host = Homo sapiens • Oseltamivir-Resistant Novel Influenza A (H1N1) Virus Infection in Immunosuppressed Patients Receiving Oseltamivir Therapy * This sequence has the H274Y mutation that might confer resistance to Oseltamivir. On August 14, 2009, this report was posted as an MMWR Dispatch on the MMWR website http://www.cdc.g ov/mmwr 9/6/2009 409

Pandemic (H1N1) 2009 Virus Antiviral Treatment • Oseltamivir: ≥1-13 year; Zanamivir: ≥7 years – Dosage varies by age and weight • Early treatment of Swine influenza – Ideally, begin treatment within 48 hours of illness onset • Duration: 5 days • Antiviral treatment may be started at any time if patient is symptomatic, not just within 48 hours of onset of symptoms • “In January 2009, the European Commission granted a Commission Decision to a type II variation (II/61) to update of section 4.2 of the SPC to provide instructions on the extemporaneous preparation of liquid formulations of Tamiflu using the contents of the 30mg, 45mg and 75mg capsules. The rational for this extemporaneous solution is that Tamiflu powder for oral suspension was developed and is approved and commercialised in the EU for children above 1 year of age and adults who cannot swallow capsules. This formulation has a shelf life of 24 months and it is anticipated that limited availability of this formulation may occur specifically in emergency situations such as an influenza pandemic or more simply when supplies of the oral suspension are not available. Development activities were undertaken to explore the feasibility of preparing extemporaneous formulations at home by the patient, parent or guardian using readily available sweetened food products to mask the bitter taste of the capsule content. This type II variation (II/61) was submitted to provide instructions in the SPC and the PL on how this liquid extemporaneous preparation should be made using the 30 mg, 45 mg and 75 mg capsules of Tamiflu. • The CHMP is now working in close collaboration with the MAH (Roche) to give practical guidance on how Tamiflu can be dosed from this extemporaneous solution to be given to children less than 1 year of age. This practical guidance should soon be agreed and released.” • Cited from: FOLLOW-UP RECOMMENDATIONS FROM CHMP ON Novel Influenza (H1N1) outbreak Tamiflu (oseltamivir) Relenza (zanamivir) EMEA/H/A-5.3/1172 Article 5(3) of Regulation (EC) No 726/2004 http://www.emea.europa.eu/humandocs/PDFs/EPAR/tamiflu/32609509en.pdf 9/6/2009 410

EMEA Dosing recommendations for antiviral chemoprophylaxis of children younger than 1 year using oseltamivir • Age Recommended prophylaxis dose for 10 days : • <3 months – Not recommended unless situation judged critical due to limited data on use in this age group • 3-5 months 20 mg once daily • 6-11 months 25 mg once daily • During a pandemic, if Tamiflu is http://www.emea.europa.eu/h umandocs/PDFs/EPAR/tamiflu/ prescribed to children under the age 32609509en.pdf of one, the recommended dosage is 2 to 3 mg per kg body weight • 9/6/2009 (EMEA May 8 report) 411

Tamiflu (Oseltamivir) for Ireland Treatment Schedule: • Containment Phase: • Adults - The following actions commence on receipt of test result of a probable or confirmed case: – Chemoprophylaxis for close contacts as (1 course = 10 days) Oseltamivir 75mg every 12 hours for 10 days – (PIEG suggests dose to be reduced by 50% if creatinine clearance is less than 30ml/minute i.e. 75mg once a day) Children Dose • Children Child aged >1yr; body weight Oseltamivir 2-3mg/kg twice daily for 5 Pandemic Influenza days Preparedness for Ireland: Advice of the Pandemic Child aged ≥1yr; body weight 15kg or Oseltamivir 30mg 12-hourly for 5 days Influenza Expert Group lower Chapter 5 Table of Contents Public Health Response: 16-23kg (3yr-<7yrs) Oseltamivir 45mg 12-hourly for 5 days Antivirals http://www.hpsc.ie/hpsc/A- 23-40kg Oseltamivir 60mg 12-hourly for 5 days Z/EmergencyPlanning/AvianPandemicInfluen za/Guidance/PandemicInfluenzaPreparednes sforIreland/File,3257,en.pdf Child 40kg or over Oseltamivir 75mg 12 hourly for 5 days 9/6/2009 412

Tamiflu (Oseltamivir) Treatment for Pandemic (H1N1) 2009 Virus for Ireland Adult dose/ pregnancy and breastfeeding mothers • Treatment for acute illness: 75 mg PO bid for 5 days • Prophylaxis: 75 mg PO once a day for 10 days – Paediatric dose – (>3 months clinical judgement for hospital admission) • Treatment for acute illness and age <1 year – 2 to 3 mg per kg once daily for 5 days • Treatment for acute illness and age >1 year – <15 kg: 30 mg PO bid for 5 days – 15-23 kg: 45 mg PO bid for 5 days – 23-40 kg: 60 mg PO bid for 5 days – >40 kg: Administer as in adults for 5 days • Chemoprophylaxis and age <1 year – 2 to 3 mg per kg once daily for 10 days – <3 months: Data limited; not recommended unless situation judged critical (Possible Hospital admission) • Chemoprophylaxis and age >1 year – <15 kg: 30 mg PO once daily or 10 days – 15-23 kg: 45 mg PO once daily or 10 days – 23-40 kg: 60 mg PO once daily for 10 days – >40 kg: Administer as in adults for 10 days • Chemoprophylaxis is no longer generally recommended for contacts • There currently is no paediatric suspension available in Ireland (See Extemporaneous Preparation) 9/6/2009 • All paediatric dosages not to exceed 10 days 413 • A supply of 75mg, 45mg and 30mg capsules is available

Tamiflu (Oseltamivir) Resources • Tamiflu (oseltamivir) Tamiflu is taken by mouth. The European Medicines Agency (EMEA) has reviewed the use of Tamiflu (ostelamivir) . The Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended that during the pandemic: – Tamiflu can be used in children younger than one year of age – Tamiflu can be used in women who are pregnant or breastfeeding • Tamiflu 75mg Capsule Summary of Product Characteristics Tamiflu 75mg Capsule Patient Information Leaflet Tamiflu Oral Suspension Summary of Product Characteristics Tamiflu Oral Suspension Patient Information Leaflet Tamiflu 30mg Hard Capsule Summary of Product Characteristics Tamiflu 45mg Hard Capsule Summary of Product Characteristics Tamiflu 30mg/45mg Hard Capsule Patient Information Leaflet 9/6/2009 414

Pandemic (H1N1) 2009 Virus Oseltamivir (Tamiflu) Adverse Effects • Metabolized by liver, excreted in urine • Very rare: • Adverse effects • Stevens-Johnson syndrome (SJS) • Gastrointestinal (nausea, vomiting) Other side effects – 300 adverse reaction/year in US may include: – Rarely associated with children with conjunctivitis • Source CDC • Headache • Diarrhoea • Toxic epidermal necrolysis (TEN) • Dizziness • Extremely Rare Neuropsychiatric disorders • Sinus inflammation • 1. Hallucinations • Epistaxis 2. Delusional behaviour • Conjunctivitis 3. Loss of contact with reality • Dyspepsia 4. Convulsions • Abdominal pain 5. Nausea and vomiting 6. Psychosis • Dosage reduction: 7. Suicidal behaviour – Kidney disease • Tamiflu can be taken with or without food, although it is recommended to take Tamiflu with food to reduce the chance of feeling or being sick (nausea or • Children (aged 1 to 12 years) vomiting) – Other less common side effects, which may also be caused by influenza, are ear inflammation, Source: PACKAGE LEAFLET: INFORMATION inflammation of the lungs, sinusitis, bronchitis, FOR THE USER aggravation of pre-existing asthma, nose bleeding, UK/Ireland/Malta 2009 ear disorders, inflammation of the skin, swelling of http://tamiflu.ie/premium- the lymph nodes, conjunctivitis, visual disturbances pages/resources/Tamiflu75mg-package.pdf and heart rhythm abnormalities. 9/6/2009 415

Oseltamivir (Tamiflu) Children Dosing Fact Sheets 9/6/2009 416

Oseltamivir (Tamiflu) Children Fact Sheets 9/6/2009 417

Relenza (Zanamivir) Treatment for Pandemic (H1N1) 2009 Virus for Ireland • Relenza administration • Two types 1. Diskhaler /Rotadisk Diskhaler /Rotadisk 2. Rotahaler/Rotacap – EMEA: As of July, ,2009, Relenza to be distributed with Rotahaler/Rotacap inhalation device during pandemic influenza Rotahaler/Rotacap 9/6/2009 418

Relenza (Zanamivir) Treatment for Pandemic (H1N1) 2009 Virus for Ireland – Adult dose , pregnancy and breastfeeding mothers • Treatment for acute illness: – 10 mg inhaled orally bid for 5 d • Chemoprophylaxis of household contact: – 10 mg inhaled orally qd for 10 d (initiate within 48 hrs) • Chemoprophylaxis for community outbreak: – 10 mg inhaled orally qd for 28 d (initiate within 5 d of outbreak) – Paediatric dose • Treatment for acute illness – <7 years: Not established – >7 years: Administer as in adults • Chemoprophylaxis in household contact of high risk group – <5 years: Not established – >5 years: Administer as in adults • Chemoprophylaxis in community outbreak – Adolescents 12-16 years: Administer as in adults 9/6/2009 419

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) Resources • Relenza - Summary of Product Characteristics (SmPCs) Relenza is taken by inhalation. The European Medicines Agency (EMEA) has reviewed the use of Relenza (zanamivir). The Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended that during the pandemic:- - Relenza can be used in women who are pregnant or breastfeeding - Relenza inhalation powder Summary of Product Characteristics Relenza inhalation powder Patient Information Leaflet 9/6/2009 420

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) Adverse Effects • Not metabolized, excreted • Irregular heart beat unchanged • Seizures • Adverse Effects • Allergic reactions like skin rash, • Other ear, nose, or throat infection itching or hives, swelling of the face, • Headache lips, or tongue • Nasal congestion • Confusion • Sinus irritation • Dizziness breathing problems • Cough • Fever • Nausea • Abnormal behaviour • Vomiting • Hallucinations 9/6/2009 Zanamivir is not recommended for persons with 421 underlying airway disease!

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) 10 Steps • The Diskhaler has three parts: • Don’t take it apart until you have looked at the step-by-step guide • The Rotadisk fits into the Diskhaler • The Rotadisk fits onto the wheel of the Diskhaler • Each of the four blisters on the Rotadisk contains a single dose of Relenza 9/6/2009 422

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) Application Steps 1 Remove the blue cover – Check that the mouthpiece is clean, inside and outside 2 Hold the white sliding tray as shown and pull it out until it stops 3 Gently squeeze the finger grips on the sides of the white tray. Remove the tray from the main body – The white tray should come out easily 4 Place a new Relenza Rotadisk on the wheel – Make sure the printed side is up, with the blisters facing downwards. The blisters fit into the holes in the wheel. 5. Push the white tray back into the main body If your not ready replace the blue cover 423 9/6/2009

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) Application Steps 6. Hold the Diskhaler horizontally • To get your dose ready to inhale: • Do this just before you inhale a dose a) Flip the lid up as far as it will go b) The lid must be fully vertical, to make sure that the blister is pierced completely c) Push the lid back down. • Your Diskhaler is now ready for use. Keep it horizontal until you have inhaled your dose • Use diskhaler immediately after set up! 9/6/2009 424

Pandemic (H1N1) 2009 Virus Zanamivir (Relenza) Application Steps 7. Don’t put the Diskhaler into your mouth yet Breathe out as far as is comfortable, keeping the Diskhaler away from your mouth – Don’t blow into the Diskhaler. If you do,you’ll blow the powder out of the Rotadisk • To prepare the next blister (the second part of your dose): 8. Pull the white tray out as far as it will go (don’t remove it completely), then push it back in again • This will turn the wheel so the next blister will appear – Repeat if necessary until a full blister is positioned under the piercing needle. – Repeat steps 6 and 7 to inhale the medicine. 9. After you’ve inhaled the full dose (normally two blisters): • Wipe the mouthpiece with a tissue and replace the blue cover. It’s important to keep the Diskhaler clean. • To replace the Rotadisk: 10. When all four blisters are empty, remove the Rotadisk from the Diskhaler and insert a new one, using steps 1 to 5. 9/6/2009 425

Zanamivir (Relenza) Fact Sheets 9/6/2009 426

Summary for Oseltamivir and Relenza Treatment for Pandemic (H1N1) 2009 Virus Final Draft for Ireland Oseltamivir Relenza – Adult dose/ pregnancy and breastfeeding mothers • Treatment for acute illness: 75 mg PO bid for 5 days – Adult dose , pregnancy and breastfeeding mothers • Chemoprophylaxis : 75 mg PO once daily for 10 days • Treatment for acute illness: – 10 mg inhaled orally twice a day for 5 days – Paediatric dose (possible hospital admission) • Treatment for acute illness and age <1 year • Post-exposure prophylaxis of household contact: – 2 to 3 mg per kg once daily for 5 days – 10 mg inhaled orally once a day for 10 d (initiate within • Treatment for acute illness and age >1 -13 year 48 hrs) – <15 kg: 30 mg PO twice a day for 5 days • Post-exposure prophylaxis for community outbreak: – 15-23 kg: 45 mg PO twice a day for 5 days – 10 mg inhaled orally once a day for 28 d (initiate within – 23-40 kg: 60 mg PO twice a day for 5 days – >40 kg: Administer as in adults for 5 days 5 days of outbreak) • Chemoprophylaxis is and age <1 year – Paediatric dose – 2 to 3 mg per kg once daily for 10 days – <3 months: Data limited; not recommended unless • Treatment for acute illness situation judged critical Hospital admission possible • Post-exposure prophylaxis and age >1 year – <7 years: Not established – <15 kg: 30 mg PO once daily or 10 days – >7 years: Administer as in adults – 15-23 kg: 45 mg PO once daily or 10 days – 23-40 kg: 60 mg PO once daily for 10 days • Post-exposure prophylaxis household contact – >40 kg: Administer as in adults for 10 days – <5 years: Not established – >5 years: Administer as in adults • Chemoprophylaxis is no longer generally recommended for contacts • Chemoprophylaxis community outbreak • There currently is no paediatric suspension available in – Adolescents 12-16 years: Administer as in Ireland • All paediatric dosages not to exceed 10 days adults • A supply of 75mg, 45mg and 30mg capsules is available Chemoprophylaxis for close contacts is not generally recommended during the treatment phase Antiviral treatment is now indicated for patients who are in a defined risk group or have clinically 9/6/2009 severe illness according to Algorithms or clinically judged high risk 427

Tamiflu (Oseltamivir) Liquid Extemporaneous Preparation • Extemporaneous Preparation: • When Tamiflu solution is not available capsules can be opened and placed in bowl with additives • Roche has provided guidelines for the extemporaneous preparation for the administration of Tamiflu dosages • Again, “oral solution is not available in Ireland!” http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflu enza/SwineInfluenza/AdviceforHealthProf essionals/AntiviralMedicines/File,3858,en. 9/6/2009 pdf 428

Guidelines for Reporting Suspected Adverse Reactions to Antiviral Medicines an Influenza Pandemic “Pharmacovigilance” • How to report? The most efficient way to report adverse reactions to the IMB in a pandemic situation is via our online reporting system at www.imb.ie 1. On-line at www.imb.ie and follow the links to ‘On-line Reporting’ to complete a Human Medicines Adverse Reaction Report 2. ‘Freepost system’ – Adverse Reaction Report Forms (yellow cards) can be obtained directly from the Pharmacovigilance Unit of the IMB or downloaded from the website under the ‘Publications section’. A supply of yellow cards/Adverse Reaction Report Forms may be requested by telephoning the Pharmacovigilance Unit of the IMB at 01-676 4971 9/6/2009 429

Guidelines for Reporting Suspected Adverse Reactions to Antiviral Medicines during Influenza Pandemic “Pharmacovigilance” Yellow card Pharmacovigilance Section, Irish Medicines Board, ) Kevin O'Malley House, Earlsfort Centre, Filled out by Public Health Earlsfort Terrace, Dublin 2, Ireland. Tel :353-1-676 4971 Fax: 353-1-634 3514 Email: 430 imbpharmacovigilance@imb.ie 9/6/2009

Pandemic (H1N1) 2009 Virus Irelands National Antiviral Stockpile (INAS) • Mobilization plans to be tested for Irish Alert Level Description National Stock Pile during this Pandemic Irish Alert Level 1 Cases only Influenza A(H1N1) 09 Virus outbreak if outside Ireland the Irish Alert Level Hits 2 (in a country or countries with or • Surveillance and monitoring must be In without place for future exercise improvements extensive Irish for mobilizations of Irelands National travel/trade links Antiviral Stockpile Irish Alert Level 2 New virus isolated in • As of Aug 5 2009 Ireland – According to HPSC clustered outbreaks have Irish Alert Level 3 Outbreak(s) in occurred but no widespread activity therefore Ireland the Irish Alert level is 3 (not formally announced) Irish Alert Level 4 Widespread activity in Ireland 9/6/2009 431

Pandemic Influenza Expert Group (PIEG) On Antivirals Irelands National Antiviral Stockpile • One million treatment packs of Oseltamivir (Tamiflu) are stockpiled • This quantity is sufficient to treat 55 % of the population and is over international trends • 63kg of the API has also been purchased – Active Pharmaceutical Ingredient (API), oseltamivir phosphate powder, should be purchased to treat young children between the ages of one and five years – Arrangements have been put in place so that API powder will be converted to paediatric capsules, which will be used for all children aged one to 11 years of age • 706,000 packs of zanamivir (Relenza) have now been ordered • This is sufficient to cover 20% of the population over the age of seven • 500,000 surgical masks, five million pairs of disposable gloves and 150,000 surgical gowns for health care providers (national stock pile in Ireland exceeds EU standards!) 9/6/2009 432

Pandemic (H1N1) 2009 Virus WHO Country Antiviral Distribution Plan 6 May 2009 • WHO headquarters stocks distributed to – – Honduras Indonesia countries. Regional stock distribution is – Kenya not included here so this is not the full list of – – Kiribati Kyrgyzstan countries receiving antivirals from WHO – Lao People's Democratic Republic globally – – Lesotho Liberia – Afghanistan – Madagascar – Angola – Malawi – Armenia – Mali – Azerbaijan – Mauritania – Bangladesh – Benin – Mexico – Bhutan – Mongolia – Bolivia – Mozambique – Burkina Faso – Myanmar – Burundi – Nepal – Cambodia – Nicaragua – Cameroon – Niger – Central African Republic – Nigeria WHO/Tom Moran – Chad – Pakistan – Comoros – Papua New Guinea WHO staff prepare boxes of – Congo – Republic of Moldova antiviral drugs for countries – Cote d´Ivoire – Rwanda – Cuba – Sao Tome and Principe May 8 2009 – Democratic People's Republic of Korea – Senegal – Democratic Republic of the Congo – Sierra Leone – Democratic Republic of Timor-Leste – Solomon Islands – Djibouti – Somalia – Eritrea – Sri Lanka – Ethiopia – Sudan – Gambia – Georgia – Tajikistan – Ghana – Togo – Guinea – Uganda – Guinea-Bissau – Ukraine – Guyana – United Republic of Tanzania – Haiti – Uzbekistan – Viet Nam 433 9/6/2009 – Yemen – Zambia – Zimbabwe

Influenza Flu Clinics for Antivirals, Vaccination, and Immunizations Process Flow Chart Queue Medical Assessment (screeners) Antivirals/ Require Antiviral Triage Contraindication Vaccination Med Consult Home, hosp, MD Antiviral/Vaccination Area Medical Orientation Post Antiviral/Vaccination Evaluation and Education Education EXIT Form collection Registration 434 9/6/2009

Influenza Vaccination Clinic Map Example: 9/6/2009 435

Performance Improvement for Irelands Antiviral Tiers and Targets • According to ECDC : An important general principle is that having stockpiles is of limited use without the agreed objectives, protocols, administration and delivery systems to accompany them. Good resource! Finding the balance Delaying the Pandemic Population Antiviral Stockpiling (Clinical Attack Rate) Interim guidance: Public health use of influenza antivirals during influenza pandemics 9/6/2009 436

Antiviral Update First Intravenous Use of Zanamivir • 17th ,Aug, 2009 • First intra-venous use of zanamivir • Media reported on a 20-year-old Australian with asthma, who survived severe pandemic (H1N1) 09, after being treated with an experimental intravenous Ivan Luong recuperates in The form of zanamivir (Relenza)from the US Austin Hospital • The drug is normally taken with an inhaler • Read the story at this hyperlink: • http://www.news.com.au/adelaidenow/story/0,22606, 25950004-5006301,00.html 9/6/2009 437

Pandemic (H1N1) 2009 Virus Guidance for Pharmacy Staff • Full Tamiflu info @ http://www.emea.europa.eu/humandocs/PDFs/EPAR/tamiflu/H-402-PI-en.pdf 9/6/2009 438

Pandemic (H1N1) 2009 Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/Adv iceforHealthProfessionals/General/File,3628,en.pdf 9/6/2009 439

Pandemic (H1N1) 2009 Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus • Standard Precautions require all HCWs to: • Standard Precautions must be applied by all HCWs to the care of all patients/clients in all healthcare settings regardless of the suspected or confirmed presence of an infectious agent. – Occupational health programme – Appropriate patient placement – Hand hygiene – Patient movement and transfer – Respiratory hygiene and cough etiquette – Use of personal protective equipment (PPE) – Decontamination of the environment – Decontamination of reusable medical equipment – Management of linen and laundry – Management of needle stick injuries – Management of waste – Management of spillages of blood and body fluids – Safe injection practices – Management of sharps 9/6/2009 440

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Key Components PRECAUTIONS Key Elements of Clinical Practices and Measures 2.2 Occupational Health Programme Standard Precautions  HCWs should self monitor their own health for influenza like symptoms (ILI)  HCWs with symptoms should not attend work and should immediately report symptoms to their line manager  All healthcare facilities should have a surveillance programme in place to monitor staff and patients for ILI. Clusters of outbreaks should be reported to the local Public Health Department. See “Protocol for Surveillance of Influenza-like Illness in Healthcare Workers during Pandemic Influenza A(H1N1)v Mitigation Phase” at www.hpsc.ie 2.3 Patient Placement Standard Precautions Home  Assess the patient with suspected or confirmed Pandemic (H1N1) 2009 by phone at home if possible Droplet Precautions GP/Primary care/Community  Place in a single room and avoid communal areas if possible. Otherwise do not place within approximately 1 metre of Contact Precautions other patients Hospital  Place patient with suspected or confirmed Pandemic (H1N1) 2009 in a single room preferably with ante room and en-suite facilities  Emergency departments without single rooms must have interim arrangements in place to prioritise transfer to an appropriate single room  Avoid communal areas and placing patient within approximately 1 metre of other patients Ambulance Refer to ambulance advice document 2.4 Hand Hygiene Standard Precautions Hand hygiene using liquid soap or alcohol hand gel/rub must be performed before and after all patient care procedures 2.5 Patient Movement and Transfer Standard Precautions External transfer Patient should wear a surgical mask outside their room It is the responsibility of the transferring facility to inform staff of the precautions required Droplet Precautions  Refer to ambulance advice document Contact Precautions Internal transfer  Minimise movement of patient from single room  Patient should wear a surgical mask outside their room  Staff should be informed of the precautions required in the receiving departments (e.g. diagnostic departments)  Avoid holding patients in communal areas (radiology etc)  HCW PPE: Wear a surgical mask and observe hand hygiene Care after death As there is a risk of blood or body fluid leakage in those who are deceased gloves, surgical mask, apron and Goggles (if splashing/spraying risk) should be worn by all handling the remains. Hand hygiene should be performed after removing PPE Where there is a risk of leakage of body fluids body bags should be used for transporting the remains Autopsy should be undertaken in a premises complying with HBN 20 Facilities for mortuary and post-mortem services, NHS Estate. During autopsy procedures HCWs should wear the PPE advised for an aerosol generating procedure (see 2.6) and comply with Health Services Advisory Committee, Safe working and the prevention of infection in the mortuary and post-mortem room, 2003 Embalming is permitted. Gloves, surgical mask, apron and goggles should be worn by morticians 9/6/2009 Viewing and touching of remains is permitted once skin cleansing/hygienic preparation is completed 441

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus Key Components PRECAUTIONS Key Elements of Clinical Practices and Measures 2.6 Respiratory Hygiene & Cough Standard Precautions As per Standard Precautions patients presenting with signs and symptoms of undiagnosed Etiquette respiratory infections should be  Identified promptly in primary care and emergency departments  Offered masks  Encouraged to maintain spatial separation, ideally a distance of approximately 1 meter, from others in common waiting areas Emergency departments and primary care facilities should:  Ensure that supplies of tissues, foot operating waste bins and hand hygiene facilities are available in all departments including waiting areas throughout the facility  Educate patients/visitors/carers on Respiratory Etiquette and Cough Hygiene using some or all of the following:  Patient information leaflets  Posters in all departments especially waiting areas See Appendix A for respiratory hygiene and cough etiquette poster. The poster can be Droplet Precautions downloaded from the following website •http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdvicefortheGeneralPu blic/RespiratoryHygiene/ 9/6/2009 442

Pandemic (H1N1) 2009 Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus Key Components PRECAUTIONS Key Elements of Clinical Practices and Measures 2.7 Personal Standard Precautions The following applies to all settings: Protective Droplet Precautions GP/Primary care/Ambulance transfer/Hospital Equipment Contact Precautions Patient should wear: (PPE)  A surgical mask when outside their single room HCWs must wear the following for: 1. Routine care  Surgical mask, Plastic Apron/Gown, Gloves (& Goggles if splashing/spraying risk)  Replace mask and all PPE if damp, wet or torn 2. Aerosol Generating Procedures  FFP2 or FFP3 mask (correctly fitted), Goggles, Long sleeved disposable gown, Gloves Refer to Aerosol Generating Procedures document and to PPE poster HCW’s when putting on and removing PPE must :  Put on and remove in the correct sequence (refer to PPE poster)  Remove gloves & apron/gown inside the single room  Remove mask in the ante room or immediately outside the single room if there is no ante room. Ensure door is closed.  Decontaminate hands immediately after removing PPE Visitors should be: Kept to a minimum Wear a surgical mask in patients room Wear gloves and apron/gown if assisting with care or in close physical contact with patient Educated on: Donning an removing PPE Hand hygiene Respiratory hygiene and cough etiquette 9/6/2009 443

Pandemic (H1N1) 2009 Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus Key Components PRECAUTIONS Key Elements of Clinical Practices and Measures 2.8 Environmental Decontamination Standard Precautions In addition to Standard Precautions: Only take essential equipment and supplies into the room. Droplet Precautions  Do not stockpile as unused stock will have to be discarded on cessation of additional precautions  Patient charts/records should not be taken into the single room Contact Precautions  The frequency and intensity of cleaning may need to be increased based on the patients level of hygiene and the level of environmental contamination  HCW’s must wear surgical mask, gloves, apron for cleaning the patients room Cleaning and disinfection Patients room  Thoroughly clean the environment and furniture and all patient care equipment daily with a neutral detergent and disinfectant (hypochlorite solution 1000 ppm) paying special attention to frequently touched sites and equipment close to the patient  On patient discharge/transfer cleaning and disinfection of the environment  Prior to initiating environmental cleaning and disinfection, all privacy, shower and window curtains must be Dishes and Eating Utensils removed and sent for laundering All disposable items including paper towels and toilet paper should be discarded All sterile and non-sterile supplies in the patient room to be discarded on patient transfer/discharge  Treatment rooms (e.g., x-ray etc)  Clean and disinfect the environment and furniture after use with a neutral detergent and disinfectant (hypochlorite solution 1000 ppm) paying special attention to frequently touched sites (door handles, bed rails etc)  Medical equipment (refer to 2.9)  Cutlery and crockery - No additional measures are required for cutlery and crockery washed in a dishwasher or wash with liquid detergent and water 2.9 Patient Care Equipment & Standard Precautions In addition to Standard Precautions: Decontamination of Medical Devices  Dedicate patient care medical devices (e.g., thermometers, sphygmomanometers, stethoscopes, glucometers) to single Droplet Precautions patient use  Use disposable equipment whenever possible Contact Precautions  Manufacturer’s instructions should be followed for cleaning and disinfecting of reusable medical equipment after use  Single use items should be disposed of after use  Bedpan/Commodes  Use a working washer disinfector at 80°C for one minute  Dedicate a commode to single patient use if no en suite available  Decontaminate commode surface after each patient use with a hypochlorite solution 1000 ppm 9/6/2009 444

Pandemic (H1N1) 2009 Virus Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic (H1N1) 2009 Virus Key Components STANDARD Key Elements of Clinical Practices and Measures PRECAUTIONS 2.10 Linen/Laundry Standard Precautions  No additional precautions necessary  As per Standard Precautions all contaminated laundry should be carefully placed in an alginate stitched or water soluble bag and then placed into a laundry bag clearly identified with labels, colour-coding or other methods prior to transport to an approved laundry capable of dealing with contaminated linen 2.11 Management of needle stick injuries (NSI) and Standard Precautions  No additional precautions necessary blood and body fluid exposure 2.12 Management Standard Precautions  No additional precautions necessary for Non Healthcare Risk and Healthcare Risk Waste of Waste  Dispose of all PPE as Healthcare Risk Waste (e.g. used masks) 2.13 Management spillages of blood and body fluids Standard Precautions  No additional precautions necessary 2.14 Safe Injection Practices Standard Precautions  No additional precautions necessary 2.15 Management of sharps Standard Precautions No additional precautions necessary 9/6/2009 445

Pandemic (H1N1) 2009 Virus Standard Precautions • Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie • See Website for download for clinicians 9/6/2009 446

Pandemic (H1N1) 2009 Virus Irish Universal Respiratory Hygiene • Pandemic Influenza Preparedness for Ireland: Advice of the Pandemic Influenza Expert Group • The following are components of a universal respiratory hygiene strategy to be adopted in all health care facilities • Read in Narration! Breaking the Chain of Infection 9/6/2009 447

Pandemic (H1N1) 2009 Virus Transmission-Based Precautions Transmission-Based Precautions Research Contact Precautions Direct and indirect contact transmission Contact precautions should be applied in addition to Standard Precautions to prevent transmission of Direct contact transmission involves skin-to-skin contact (such as hand-to-hand) between an infected highly transmissible organisms that are transmitted from person to person via the contact route (e.g. person and a susceptible person. Methicillin resistant Staphylococcus aureus) The proportion of influenza virus transmission caused by direct or indirect contact remains unknown; however, transmission by these routes can occur. Influenza viruses can live for 24 to 48 hours on nonporous environmental surfaces and less than 12 hours on porous surfaces (see References: Bean 1982), indicating that transmission can occur when hands that touch contaminated surfaces subsequently come into contact with oral, ocular, or nasal mucosa. Fomite transmission appears to be rare. Droplet Precautions Droplet transmission Droplet Precautions should be applied, in addition to Standard Precautions, to prevent transmission of Influenza viruses are predominantly transmitted by large droplets (ie, >5 mcm). highly transmissible organisms that are transmitted via respiratory secretions from one person to Droplets are expelled by coughing and sneezing and generally travel through the air no more than 3 feet another (e.g. Influenza) from the infected person. Transmission via large droplets requires close contact between the source and recipient persons, permitting droplets, which do not remain suspended in the air, to come into direct contact with oral, nasal, or ocular mucosa. Special air handling and ventilation systems are not required to prevent droplet transmission. Airborne Precautions Airborne transmission Airborne Precautions should be applied, in addition to Standard Precautions, to prevent transmission of Airborne transmission of influenza viruses (ie, transmission via droplet nuclei [<5 mcm], which remain highly transmissible organisms that are transmitted via the air from one person to another (e.g. suspended in the air and have the potential to travel farther than several feet) has been suggested in Tuberculosis) several reports, although evidence to conclusively support airborne transmission of influenza virus is limited (see References: Bridges 2003). Available data suggest that airborne transmission does not play a major role in the spread of influenza viruses (see References: Brankston 2007). However, airborne transmission of influenza viruses may occur, at least over short distances (see References: Tellier 2006), and further study is needed to determine the importance of this mode of transmission in healthcare or other settings. Aerosol-generating Procedures(AGPs) Aerosol-generating Procedures (AGPs) eg, intubation, bronchoscopy, nebulizer treatments) theoretically could promote dissemination of droplet nuclei from infected patients, although this has not been studied for influenza. There is no evidence to date that droplet nuclei containing influenza viruses can travel through ventilation systems or across long distances, such as can occur with tuberculosis and certain other viral agents. 9/6/2009 448

Pandemic (H1N1) 2009 Virus YOUR 4 MOMENTS FOR HAND HYGIENE (Canadian) 1. Clean your hands when 2, Clean your hands entering before touching the patient or any object or immediately before any furniture in the patient’s aseptic procedure. environment. To protect the patient To protect the patient/ patient against harmful organisms, environment from harmful including the patient’s own organisms carried on your organisms, entering his or hands her body. 4. Clean your hands when 3. Clean your hands leaving after touching immediately after an patient or any object or exposure risk to body fluids furniture in the patient’s (and after glove removal). environment. To protect yourself and the To protect yourself and the health care environment from health care environment harmful patient organisms. from harmful patient See WHO Hygiene Protocol organisms witch has 5 Steps Irish has 6 Steps 9/6/2009 449

The “My 5 Moments for Hand Hygiene” Approach (WHO) 9/6/2009 450

Irelands Hygiene “5 Step” Protocol • Ireland In 2006-9, Ireland organised a national campaign called ‘Clean Hands Save Lives’. Hand Hygiene Opportunity Definition and examples 1. Before touching a patient This is defined as any opportunity prior to patient care or entering a patient bed space (inside curtains or into a single room) to undertake any element of care such as; shaking hands clinical examination & taking clinical observations (temperature, pulse, blood pressure) adjust equipment resuming care if interrupted (e.g. called to phone) Note Avoid double counting – should a HCW immediately move from one patient to another having decontaminated their hands this is classed “after patient care “opportunity and not a missed “before patient care opportunity” 2. After touching a patient This HHO is defined as any opportunity following any physical contact with a patient such as: clinical examination or taking clinical observations (temperature, pulse, blood pressure) shaking hands assisting with food and drink 3. After body fluid exposure risk This HHO is defined as any opportunity following any procedure that may result in exposure to blood or body fluids such as: venepuncture, oral hygiene, after handling contaminated dressings blood and body fluid spillages including emptying bedpans/urinals/commodes, urine bags any contact with urinary catheters, tubing or urinary collection bag suctioning or aspiration of any body fluids after removing gloves before moving from a contaminated body site to a clean body site during patient care 4. Before clean/aseptic procedure This HHO is defined as any opportunity prior to commencing a clean or aseptic procedure such as; wound dressing catheter insertion or prior to accessing a IV catheter prior to preparation medications 5. After touching patient surroundings This HHO is defined as leaving the patient bed space (i.e. curtained areas or single room) after touching any item such as: bed or bed linen furniture (e.g. locker, chair, bed table, procedure/night light) curtains medical equipment (infusion pumps, drip stands, trolley etc) case notes before moving from a contaminated body site to a clean body site during patient care 9/6/2009 451

Hand Hygiene Compliance for Ireland Overview • A hand hygiene episode is defined as hand washing with soap and water or using an alcohol gel/rub. Compliance is defined as the total observed hand hygiene episodes divided by the HHO multiplied by 100 and expressed as a percentage. Compliance = observed hand hygiene episodes x 100 = % compliance hand hygiene opportunities (HHO) • Acute healthcare facilities (HCF) are advised to undertake hand hygiene observational audits biannually • A local action plan to address compliance rates <75% should be put in place in each HCF. This target (75%) should be viewed as the start of a process which will see it increase year on year • The overall aim of this process is to achieve 100% compliance • 9/6/2009 452

Hand Hygiene Compliance Observation Tools • The advantages of direct • Disadvantages of direct observation are: observation are: Assessment of compliance Labour intensive and time rates in different groups of consuming HCWs Requirement for trained Assessment of HCW behaviour observers (e.g., when and where HCWs Influence of the “Hawthorne are more likely to wash their effect” on results hands) Objectivity of the observer Assessment of hand hygiene Using results to compare technique internally or externally when the inter rater reliability has not been assessed 9/6/2009 453

Hand Hygiene Compliance In Acute Hospitals in Ireland 9/6/2009 454

Hand Hygiene Compliance HPSC/HSE Resources “HCAI” for Ireland • Further information from HSE on infection control and healthcare associated infection (HCAI) is available at: • Guidelines for hand hygiene in Irish healthcare settings are available at: – http://www.ndsc.ie/hpsc/A-Z/Gastroenteric/Handwashing/Guidelines/ • A suite of tools and resources on hand hygiene are available from the WHO at: – http://www.who.int/gpsc/5may/tools/en/index.html • Further information on infection control and healthcare associated infection is available at: – http://www.hpsc.ie/hpsc/A-Z/MicrobiologyAntimicrobialResistance/InfectionControlandHealthcare- AssociatedInfection/ • Alcohol Hand Rub Consumption in Acute Irish Hospitals2006 to Q4 2008 – http://www.ndsc.ie/hpsc/A-Z/Gastroenteric/Handwashing/Guidelines/ • Hand Hygiene Observation Audit tool Standard Operating Procedure – http://www.ndsc.ie/hpsc/A-Z/Gastroenteric/Handwashing/AuditTools/File,3789,en.pdf – Hand hygiene observational audit tool 2009 (Excel template) – Hand hygiene compliance - Epi Insight, Volume 10, Issue 7, July 2009 • External Links • Hand Hygiene in Healthcare Settings, CDC, US • Hand Hygiene Resource Center • HandHygiene.co.uk “You can hyperlink during slide show to view and download files!” 9/6/2009 455

Performance Improvement Pandemic Planning “Hand Washing” • Author promotes this hand wash technique with incorporating times/wash • 20-30 seconds for non-soiled hands • 60 seconds for visibly soiled hands 9/6/2009 456

Pandemic (H1N1) 2009 Virus Protocol for Surveillance of Influenza-like Illness in Healthcare Workers during Pandemic Influenza Containment Phase 7.0 Mitigation Phase 9.0 • http://www.hpsc.ie/hpsc/A- http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/S Z/EmergencyPlanning/AvianPandemicInflu wineInfluenza/AdviceforHealthProfessionals/Hos enza/SwineInfluenza/AdviceforHealthProfe pitalClinicians/File,3638,en.pdf 9/6/2009 ssionals/HospitalClinicians/ 457

Pandemic (H1N1) 2009 Virus “Protocol for Surveillance of Influenza-like Illness in Healthcare Workers during Pandemic Influenza A(H1N1)v “Mitigation Phase” Mitigation Phase 9.0 • Health Protection Surveillance Centre 25-27 Middle Gardiner St Dublin 1, Ireland. t: +353 1 8765300 f: +353 1 8561299 e: hpsc@hse.ie See Website for download for clinicians or this hyperlink http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/S wineInfluenza/AdviceforHealthProfessionals/Hos pitalClinicians/File,3638,en.pdf 9/6/2009 458

Pandemic (H1N1) 2009 Virus Surveillance of Healthcare Workers • Healthcare worker (HCW) • Porters includes: • Domestic staff • Hospital clinician teams • Receptionists • General practitioners • Administration staff • Nurses • Ambulance staff • Laboratory scientists • Mortuary workers • Physiotherapists and other allied health professional • Healthcare students • Health volunteers and community health workers Safety, Health and Welfare at Work Act 2005 9/6/2009 459

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus • Unusual clusters or syndromes • If there are unusual clusters of disease or syndromes among HCWs – The DPH/MOH will immediately inform HPSC of any unusual clusters of disease or syndromes among Healthcare workers July ,16 , 2009 update “WHO” Definition of a healthcare cluster: A cluster is defined as two or more healthcare workers in the same healthcare facility/unit with unexplained acute respiratory illness and with fever ≥38°C, or with severe lower respiratory tract infection or pneumonia, and with onset of illness within a period of 14 days of each other. 9/6/2009 460

Pandemic (H1N1) 2009 Virus Surveillance of Healthcare Workers Clinical Criteria • Acute onset of fever (temperature > 38 °C or history of fever and two or more of the following: • Cough Containment Phase Mitigation Phase Mitigation Treatment Phase • Sore throat • Myalgia • Headache • Rhinorrhea • Vomiting/Diarrhoea HPSC June ,26, 2009 HPSC July ,16, 2009 HPSC July ,29, 2009 • Pneumonia Progression of GP algorithms • Influenza-like Illness (ILI) • Severs respiratory illness with suspected/probable pneumonia (SRI) • Acute Respiratory Distress Syndrome (ARDS) 9/6/2009 461

Comparison of Community and Healthcare Cluster Definitions Definition Community Surveillance Definition of a healthcare cluster of Clusters/Outbreaks (World Health Organization) • Influenza-like illness (ILI) - • A cluster is defined as two or definition for interim surveillance more healthcare workers in the of clusters/outbreaks same healthcare facility/unit with • Three or more cases of ILI arising within the same 72 hour period unexplained acute respiratory which meet the same clinical case illness and with fever ≥38°C, or definition and where an with severe lower respiratory epidemiological link can be tract infection or pneumonia, and established with onset of illness within a • ILI symptoms include: – Acute onset of fever (temperature period of 14 days of each other ≥38°C) – OR history of fever – AND flu-like illness (two or more of the following symptoms: cough, sore throat, myalgia, headache, rhinorrhea or vomiting/diarrhoea) 9/6/2009 462

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus • Report to occupational health department • The relevant line manager should notify the occupational health department: • If there is an apparent increase in absenteeism rates among a particular group of HCWs or in a particular area • If there is an apparent cluster of acute respiratory illness among a particular group of HCWs or in a particular area • If a HCW becomes ill with a severe lower respiratory tract infection or pneumonia • In institutions where there is no Occupational Health Physician, the General Manager will consult with the Chair of the Medical Executive to assign this role to a suitable doctor. See also Supplement 10, Guidance for Pandemic Influenza: Infection Control in Hospitals, Community and Primary Care Settings available at: • http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/Guidance/PandemicInfluenzaPrepared nessforIreland/ 9/6/2009 463

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus • Single cases (Containment Phase) • If a HCW is admitted to hospital with respiratory symptoms of ILI (Influenza-like-Illness), AFRI (acute febrile respiratory illness) or severe lower respiratory illness/pneumonia and they have at least one of the following in the seven days before disease onset: – Been a close contact of a confirmed case of Pandemic Influenza A(H1N1) 09 Virus infection while the case was ill – Have travelled to an area where sustained human-to- human transmission of Pandemic Influenza A(H1N1) 09 Virus is documented – Worked in a laboratory – Are within the defined risk groups that includes pregnant women, people on medication for asthma, Update June 11 2009 http://www.hpsc.ie/hpsc/A- and bariatric (obese) individuals with a BMI ≥40 Z/EmergencyPlanning/AvianP andemicInfluenza/SwineInflu enza/AdviceforHealthProfessi onals/GPs/File,3724,en.pdf 9/6/2009 464

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Containment Phase continues • If a HCW has been involved in caring for or examining a symptomatic patient with Pandemic Influenza A(H1N1) 09 Virus infection the following actions should be taken: • 1.Inform the regional DPH/MOH if the HCW provided direct clinical or personal care or examined the symptomatic patient without appropriate Personal Protective Equipment (PPE). Discuss contact management with DPH/MOH • 2.For HCWs who are defined in the high risk category or and did not wear PPE* while caring for symptomatic patient: – Institute post-exposure prophylaxis with oseltamivir (Tamiflu) as soon as possible unless more than 7 days have elapsed since the last exposure. The dose of oseltamivir is 75mg daily for 10 days following last exposure • 3.Provide all HCW contacts with clear public health recommendations and information on Pandemic Influenza A(H1N1) 09 Virus (available at www.hpsc.ie/hpsc/) 9/6/2009 465

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Containment Phase continues • 4. Request that any febrile respiratory or other unexplained illness within 7 days of last contact be reported • 5. If the HCW contact becomes unwell they should be investigated and treated by there GP and occupational health (liaise with DPH/MOH) • They should also be advised to discontinue work immediately and upon return be medically cleared • 6. Advise all contacts to strictly adhere to all infection control and prevention precautions as follows: – Avoid touching their faces, including their eyes and nose and mouth with their hands – Wash hands frequently. This means washing with soap and running water for a minimum of 15-30 seconds or the use of an alcohol-based hand sanitiser (minimum 60% alcohol) if the hands are not visibly soiled – If visible soiled use WHO guidance for visible soiled hand wash technique (60 seconds/hand wash) – Cover their mouth with a tissue when they cough and/sneeze, and dispose carefully in a bin afterwards 9/6/2009 466

Pandemic (H1N1) 2009 Virus Occupational Health Role • The previous occupational health mitigation slides were cited from the “Protocol for Surveillance of Influenza- like Illness in Healthcare Workers during Pandemic Influenza A(H1N1)v Mitigation Phase” by HPSC ver. 9.0 • Available for download at HPSC • http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInflue nza/AdviceforHealthProfessionals/OccupationalHealthProfes sionals/File,3638,en.pdf 9/6/2009 467

Pandemic (H1N1) 2009 Virus Infection Control In Health Care Setting • For visible soiled hands WHO recommends the following technique 9/6/2009 468

Healthcare Workers with Probable Pandemic (H1N1) 20 09 Virus Occupational Health Role Update July, 16, 2009 • “Close contacts in the health care setting are defined as: health or social care workers who provided direct clinical or personal care or who examined a symptomatic patient (including taking nasal and throat swabs for viral testing) without wearing appropriate personal protective equipment (PPE) for Standard, Droplet and Contact Precautions: – Routine care (including taking nasal and throat viral swabs): surgical mask, gloves, plastic apron (and goggles if risk of splashing or spraying) – Aerosol generating procedures: FFP2 or FFP3 masks, goggles, long-sleeved gown and gloves. – Failure to implement hand hygiene following contact with contaminated surfaces or after removing PPE is also considered to pose risk of infection. – Casual contact with the ill person for example, passing them in the corridor at work or waving to them etc. does not mean you are a contact and does not require any further action. • The following groups of healthcare workers caring for patients with probable/confirmed Pandemic Influenza A(H1N1) 09 Virus ) will require a risk assessment and consideration of chemoprophylaxis: – Healthcare workers who have not worn appropriate PPE – Healthcare workers who have worn PPE without formal fit testing – Healthcare workers who have worn surgical masks but who have been unwittingly exposed to patient generated aerosols” 9/6/2009 Cited from HPSC 469

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Surveillance • The Occupational Health team (or as per local arrangements) will inform Public Health about details of contacts • A Public Health Doctor will contact you to ask you a number of questions about your health and the amount / type of contact which you had with the sick person, and will advise on what precautions you need to take • In hospitals, where there is an Occupational Health Department, this will be carried out by Occupational Health staff 9/6/2009 470

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Surveillance • Containment Phase • Health or social care workers who provided direct clinical/personal care or who or who examined a symptomatic patient without wearing appropriate PPE** – Those who were wearing appropriate PPE should self monitor for one week and report symptoms as explained in Public PEP Phase 6 Update Health Management of Contacts June, 22, 2009 9/6/2009 471

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Surveillance • Containment and Mitigation Phase: • All healthcare workers at this time should be self monitoring for flu-like symptoms and should report the development of same to their line manager promptly • HCW contacts of suspected or Pandemic Influenza A(H1N1) 09 Virus should check their temperature twice a day and look out for flu-like symptoms for a period of 7 days: • Acute sudden onset of fever developing in <6 hours (temperature ≥38C) or history of fever • and two or more of the following: – cough, sore throat, myalgia, headache, rhiorrhoea or diarrhoea, vomiting – OR – Pneumonia or other severe respiratory illness • Please report the development of any flu like symptoms to public health staff and to your line manager promptly • You will also be asked to contact Occupational Health and referred to your GP or emergency department physician 9/6/2009 472

Healthcare Workers “Fitness for Work” Occupational Health Role • Containment and Mitigation Phase: • Fitness for Work • Occupational health advice on fitness for work (or on the need for work restrictions at a given time) should be sought by: • Healthcare workers who develop symptoms of ILI (Influenza Like Illness), who should report to their line manager in the first instance • Healthcare workers recovering from ILI • Healthcare workers who have been in unprotected contact with suspect or confirmed cases of ILI (either in the community or at work) • Healthcare workers who have been prescribed antiviral therapy by their GP or a Public Health Doctor • Healthcare workers who have pre-existing medical conditions which might increase their risk of severe influenza complications • Pregnant healthcare workers • Healthcare workers who cannot achieve an adequate ‘seal’ with the PPE provided by their employer 9/6/2009 473

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Mitigation Phase: • Occupational Health Role • If a HCW has been involved in caring for or examining a symptomatic patient with probable or confirmed influenza A(H1N1)v infection the following actions should be taken: • Provide all HCW contacts with clear public health recommendations and information on influenza A(H1N1)v (available at www.hpsc.ie/hpsc/). • Request that any febrile respiratory or other unexplained illness within 7 days of last contact be reported. • If the HCW contact becomes unwell they should contact their GP and Occupational Health as soon Interim algorithm for the PRIMARY CARE Management of Persons who may have Influenza A(H1N1)v as possible and go off duty until medically assessed. 9/6/2009 474

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Mitigation Phase: • Single cases and unusual clusters or syndromes should be notified as follows: • If a HCW is admitted to hospital with respiratory symptoms suggestive of influenza A(H1N1)v, the staff member’s GP and Occupational Health should be notified immediately. • If there are unusual clusters of disease or syndromes among HCWs, the Occupational Health Department and DPH should be informed as soon as possible. • The DPH/MOH will immediately inform HPSC of any unusual clusters of disease or syndromes among HCWs. 9/6/2009 475

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Mitigation Phase: • Report to Occupational Health Department • The relevant line manager for healthcare staff should notify the Occupational Health Physician and Occupational Health Nurse Advisors or the doctor assigned to this function in healthcare facilities with no Occupational Health staff: • If there is an apparent increase in absenteeism rates among a particular group of HCWs or in a particular area of the healthcare facility • If there is an apparent cluster of acute respiratory illness among a particular group of HCWs or in a particular area of the healthcare facility • If a HCW becomes ill with a severe lower respiratory tract infection or pneumonia. • In the case of medical staff, it is recommended that all Clinical Consultants notify Occupational Health of any ILI or respiratory illness in medical members of their clinical teams. 9/6/2009 476

Healthcare Workers with Probable Pandemic (H1N1) 2009 Virus Occupational Health Role • Mitigation Phase: • Education of healthcare workers • The hospital influenza pandemic committee should arrange for all HCWs to receive education on: • The signs and symptoms of influenza A(H1N1)v • Whom to notify i.e. line manager if they suspect they may be suffering from any of the relevant symptoms or clinical conditions • Infection prevention and control precautions to adhere to, such as: – Avoid touching their faces, including their eyes and nose and mouth with their hands – Wash hands frequently. This means washing with soap and running water for a minimum of 15-20 seconds or the use of an alcohol-based hand sanitiser (minimum 60% alcohol) if the hands are not visibly soiled – Cover their mouth with a tissue when they cough and/sneeze, and dispose carefully in a bin afterwards 9/6/2009 477

Point of Care Risk Assessment Tool for Pandemic (H1N1) 2009 Flu Virus (Risk Assessment Matrix) One goal of this guidance is, using a risk assessment approach, to support use of personal protective equipment most appropriate to the risk associated with the care to be provided, thereby protecting limited resources for those situations where protection is most needed.

Point of Care Risk Assessment Tool for Pandemic (H1N1) 2009 Flu Virus • According to PHAC: • “Source control, achieved through administrative and engineering measures, is the most effective way to prevent the transmission of infectious agents, including H1N1 2009, in all health care settings” • This Interim Guidance is designed to help slow (mitigate) the transmission of this virus • The following guidance should be read in conjunction with relevant HPSC guidance documents.

Point of Care Risk Assessment Tools • The PCRA tool consists of tables 1 to 4. • Step 1: In Table 1, choose one of the physical setting and level of patient interaction options (in the highlighted column) using the description and example columns in the table • Step 2: In Table 2, choose one of the patient clinical status and source control capability options (in the highlighted column) using the description and patient presentation column in the table • Step 3: Using the matrix on Table 3, match the physical setting and level of patient interaction option from Table 1 (Step 1) with the patient clinical status and source control capability option identified from Table 2 (Step 2), to determine the appropriate level of precautions • Step 4: From Table 4, determine what specific measures and personal protective equipment are indicated for the level of precautions identified in Table 3 (Step 3)

Table 1: Identification of the Physical Setting and Level of Patient Interaction Physical Setting and Level of Patient Description Example Interaction No Patient Interaction, Area with no patient access (restricted areas) Non-clinical setting (medical record Non-Clinical department, administrative office, central pharmacy, information technology office, central storage area, mail room, central maintenance areas, business office, etc.). No Direct Patient Interaction and No Indirect No face-to-face interaction and no indirect Hallways, cafeteria, public areas, clinical Contact contact with patients. areas with no patient access (charting room, office, storage room, staff lounge, medication room, etc.), totally enclosed reception/triage areas with physical barrier between HCW and patient. Indirect Contact No direct patient interactions; Indirect Discharge patient room cleaning, equipment contact only with patient environment or cleaning. contaminated inanimate objects Direct Patient Interaction Direct, face-to-face interaction with patient Providing patient care, home care visit, (within 2m of the patient) assisting with Activity of Daily Living (ADL), diagnostic imaging, phlebotomy services, physiotherapy, occupational therapy, recreational therapy, intra-hospital transport/portering, non-enclosed triage/registration area, cleaning patient bedspace while occupied, routine ambulance or inter-facility transport Direct Patient Interaction with Potential for Performing and/or assisting with Aerosol Open endotracheal suctioning, Aerosol Generation Generating Medical Procedures (AGMP) bronchoscopy, endotracheal intubation, tracheostomy procedures, nebulized therapy, cardiopulmonary resuscitation

Table 2: Identification of the Patient Clinical Status and Source Control Capability Patient Clinical Status and Source Description Patient Presentation Control Capability Recovered from Influenza Patient recovered from influenza Influenza-infected patient, beyond the known period of communicability Influenza and Compliant or Weak 1) Patient with symptoms Cough of any intensity and Cough and Not Compliant compatible with influenza Adherence with respiratory with cough hygiene Adherence to hand hygiene 2) Patient with symptoms Weak or no cough and Not compatible with influenza adherent with respiratory with weak or no cough hygiene Not adherent to hand hygiene Influenza and Forceful Cough and Patient with symptoms Forceful cough and Not adherent Not Compliant compatible with influenza with respiratory hygiene Not adherent to hand hygiene Influenza and AGMP Patient with symptoms And an Aerosol Generation compatible with influenza Medical Procedure (AGMP) is being performed Note: If more than one risk level identified (e.g., multiple concurrent patient interactions), select the higher risk level.

Table 3: Level of Precautions Matrix Patient Clinical No Patient No Direct or Indirect Contact Direct Patient Direct Patient Status and Source Interaction Indirect Patient Interaction Interaction with Control Capability Non Clinical Interaction AGMP Recovered from I I II II II Influenza Influenza and I I II III IV Compliant or Weak Cough and Not Compliant Influenza and I I II III IV Forceful Cough and Not Compliant Influenza and I I III IV IV AGMP Note: It is anticipated that the majority of patients with H1N1 2009 will be cared for using level II and III and a minority would be cared for using level IV precautions. AGMP- Aerosol Generating Procedures

Table 4: Personal Protective Equipment Suggested for the Level of Precautions for Human Cases of H1N1 2009 Hand hygiene Respiratory FFP2/3 Surgical Mask Eye Gown Gloves hygiene Respirator Protection Mask Level I Yes Yes No Patient No Patient No Patient No Patient No Patient Contact – Contact – Contact – Contact – Contact – Not Required Not Required Not Required Not Required Not Required Level II Yes Yes No, Except as As Per As Per As Per As Per per Routine Routine Routine Routine Additional Practices Practices Practices Practices Precautions Level III Yes Yes No, Except as Yes Yes As Per As Per per Routine Routine Additional Practices Practices Precautions Level IV Yes Yes Yes No Yes As Per As Per Routine Routine Practices Practices Note: Additional Precautions recommend an FFP-2-3 respirator mask for known or suspected active tuberculosis, measles, shigellosis or where droplet or airborne precaution are necessary according to hospital infection control policies (Adapt kardex/care plan to state exposure risk!)

Pandemic (H1N1) 2009 Virus Personal Protective Equipment PPE • PPE = Personal Protective Equipment • PPP = Personal Protective Practices • PPE + PPP = Prevention Personal Protection is not just “personal”: It is also about preventing spread of disease to others! 9/6/2009 485

Recommended Initial PPE Protection Levels AGENT CATEGORY MINIMUM LEVEL OF PROTECTION UNKNOWN LEVEL A NERVE LEVEL A(1) BLISTER LEVEL A(2) BLOOD LEVEL B(3) CHOKING LEVEL B(3) BIOLOGICAL High Efficiency Particulate Air FILTER w/LEVEL C RADIOLOGICAL High Efficiency Particulate Air FILTER w/LEVEL C (1) High concentrations may result in nerve agent poisoning (2) Sufficient vapor will cause blisters (3) Level A may be required in an enclosed area 9/6/2009 486

Pandemic (H1N1) 2009 Virus Personal Protective Equipment PPE • Avian flu indicated that using a face mask with a rating of N99, N100 or P100 in the United States • A rating of FFP3 in Europe should be effective in protecting against transmission FFP3 – 99% efficiency Respirator Mask • N95 or FFP2 face masks provide about 94% efficiency Particle Recent work by Viscusi5 suggests that most N95 Respirator N95 (FFP2) respirators stored in warehouse and laboratory conditions are likely to maintain there filtration capacity for up to 10 years 9/6/2009 487

Aerosol Generating Procedures (AGP) According to WHO • Aerosol generating procedures: • Nebulisation • Intubation and related • Non-invasive positive procedures, e.g. manual pressure ventilation ventilation • Bi-level positive airway • Respiratory and airway suctioning pressure (BiPAP) ,CPAP,NIV (including tracheostomy care) • High frequency oscillating • Nasopharyngeal aspiration ventilation • Cardiopulmonary resuscitation • Bronchoscopy • Nasopharyngeal aspirate • Transtracheal aspirate • Broncheo-alveolar lavage • Biopsy of lung or tracheal tissues • Autopsy procedures – i.e.. (Oscillating saws) Documented transmission Non- documented transmission 9/6/2009 488

Pandemic (H1N1) 2009 Virus HealthCare Environmental Waste • In aerosol generating activities (e.g., collection of clinical specimens, endotracheal intubation, nebulizer treatment, bronchoscopy, and resuscitation involving emergency intubation or cardiac pulmonary resuscitation) SOP must be in place • Appropriate disinfectants – 70% Ethanol – 5% Lysol – 10% Bleach http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenz a/SwineInfluenza/AdviceforHealthProfessiona ls/InfectionControl/File,3625,en.pdf • According to PIEG: Commonly used surfaces such as door handles, handrails, table surfaces etc. should be cleaned first and then disinfected with a chlorine releasing disinfectant (1000 ppm) twice daily. 9/6/2009 489

HPA-Recommendations For Extending The Lifespan Of Masks: • Use out-of-date facemasks and respirators to the extent available • Use lower grade respirators to the extent available (where a respirator is indicated) • Out-of-date but in-grade respirators are preferred to incorrect grade but in-date stock • Layered facemasks might be considered as a last resort when no respirators (of any grade) are available for the performance of aerosol generating procedures however this will impact on the supply of facemasks for other uses • Re-use of any device is not recommended except as absolute last resort • Decontamination of facemasks is not recommended • Experimental work suggests that high efficacy respirators can be decontaminated without degradation using certain regimens, but these are unlikely to prove practical and there are insufficient data to be certain of a reliable effect. This should only be considered if practical and then as a measure of last resort • Hospitals can perform individual risk assessments to minimise all but essential non-pandemic use of facemasks and determine whether alternatives measures could be adopted • Masking patients with a facemask as an alternative to masking HCWs might be a more efficient use of limited quantities of masks in certain circumstances • Any other nose/mouth covering could be considered once facemask are exhausted, but there are no data in support of specific items other than the DIY 9/6/2009 490 cotton mask described by Dato et al

Pandemic (H1N1) 2009 Virus Personal Protective Equipment PPE • Disposable particulate respirators (e.g. NIOSH N95 or European EN149: 2001 • FFP2; NIOSH N99 or European EN149: 2001 FFP3; or NIOSH N100) • Must have Fit Testing Program FFP2 9300 valved disposable respirator FFP3 valved moulded cup mask 9/6/2009 491

Pandemic (H1N1) 2009 Virus Respiratory Protection Programme • Example 9/6/2009 492

Pandemic (H1N1) 2009 Virus Respiratory Protection Programme • A respiratory protection programme for staff advised to wear respirators should be provided by each healthcare facility to ensure compliance with the following health and safety legislation and standards:  Safety, Health and Welfare at Work Act, 2005  Safety, Health and Welfare at Work (General Application) Regulations 2007 (S.I. No. 299 of 2007). Chapter 3 of Part 2: Personal Protective Equipment  Safety, Health and Welfare at Work (Biological Agents) Regulations 1994 (S.I. No. 146 of 1994) (as amended by S.I. 248 of 1998).  IS EN 529:2005 (Irish Standard on Respiratory Protective Devices) 9/6/2009 493

Pandemic (H1N1) 2009 Virus Respiratory Protection Programme • Governance: • Identify department responsible to deliver the respiratory protection programme • Identify personnel responsible for the implementation of the respiratory protection programme • Allocation of resources to deliver the programme • Selection, purchase and supply of suitable masks to each healthcare facility • Storage and maintenance of equipment • Disposal of used equipment • Record keeping 9/6/2009 494

Pandemic (H1N1) 2009 Virus Respiratory Protection Programme • Theoretical information, training and instruction including: • Types of risk • Knowledge and understanding of respiratory equipment including limitations • Personal factors including medical conditions, improper fitting • Fit testing and fit checking • Practical training including: • An initial fit test using qualitative/ quantitative methods • Ongoing fit check to confirm the seal each time the mask is donned • Donning, removing and disposing of mask 9/6/2009 495

Pandemic (H1N1) 2009 Virus Respiratory Protection Programme • Persons with excessive facial hair, the following options may be considered: • HCW agrees to remove the beard / facial hair • HCW agrees to be otherwise deployed • Pre-exposure prophylaxis (with antiviral medication) be considered • Use of powered air respirator be considered • If none of these options is deemed Types of respirators that can be fit tested with this method include: appropriate or possible (and only in • Filtering facepieces FFP1, FFP2, FFP3; exceptional circumstances) a bearded HCW • Half facemask respirators fitted with a particulate or combined filter may proceed in the clinical care of such patients, only having been fully informed of the risks and in the knowledge that an FFP2 or FFP3 respirator cannot ensure adequate protection 9/6/2009 496

Pandemic (H1N1) 2009 Virus Personal Protective Equipment (PPE) • Pandemic Influenza A(H1N1) 09 Virus: • Infection Prevention and Control Precautions for use when caring for patients with suspected or confirmed Pandemic Influenza A(H1N1) 09 Virus http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflue nza/SwineInfluenza/AdviceforHealthProfessi onals/AmbulanceStaff/File,3627,en.pdf 9/6/2009 497

How To Perform a Particulate Respirator Seal Check 9/6/2009 498

Donning and Doffing Personal Protective Equipment (PPE) Donning PPE Doffing PPE 9/6/2009 499

Pandemic (H1N1) 2009 Health Professionals (PPE) • Pending clarification of transmission patterns for this virus, personnel providing direct patient care for suspected or Pandemic Influenza A(H1N1) 09 Virus cases should wear a fit-tested FFP2 9300 valved disposable disposable FFP2-3 respirator respirator mask • Fit-tested disposable FFP2-3 respirator and eye protection (e.g., goggles; eye shield), disposable non-sterile gloves, and gown, when coming into close contact with the swine influenza 9/6/2009 FFP3 valved moulded cup mask 500

Pandemic (H1N1) 2009 Mortuary (PPE) • However, for people who must directly handle remains, such as recovery personnel, or persons identifying remains or preparing the remains for burial or cremation, there can be a risk of exposure to Pandemic Influenza A(H1N1) 09 Virus • Fit-tested disposable FF3 respirator and eye protection (e.g., goggles; eye shield), disposable non-sterile gloves, and gown, when coming into close contact with the fatalities • Increase level of protection if needed! 9/6/2009 501

Pandemic (H1N1) 2009 Virus Handling Human Remains (HHR) • Potentially contaminated human remains must be segregated from the general population of a hospital or other facility as soon as the risk is recognized • Only those wearing the appropriate level of PPE should perform segregation of contaminated human remains • Segregation involves: • Placing the human remains along with all personal effects and clothing into an impermeable body bag • Attaching available identifying information to the body and bag • Moving the bagged human remains to a secure holding area • Notifying the medical examiner of the circumstances of the death, and releasing the human remains to personnel designated by the medical examiner • Autopsy should be undertaken in a premises complying with HBN 20 Facilities for mortuary and post-mortem services, NHS Estate • During autopsy procedures HCWs should wear the PPE advised for an aerosol generating procedure and comply with Health Services Advisory Committee, Safe working and the prevention of infection in the mortuary and post- mortem room, 2003 9/6/2009 502

Pandemic (H1N1) 2009 Virus Handling Human Remains Health Care setting • Pandemic Influenza A(H1N1) 09 Virus handling of Human Remains Civil Registration Act 2004. Pt.5 Provision of particulars, and registration, of deaths. 9/6/2009 503

Pandemic (H1N1) 2009 Virus Handling Human Remains (HHR) • Family Contact with the Deceased in Health Care Settings • For deceased persons with confirmed, probable, or suspect Pandemic (H1N1) 2009 Virus consider limiting contact with the body in health care settings to close family members • Viewing and touching of remains is permitted once skin cleansing/hygienic preparation is completed! 9/6/2009 504

Pandemic (H1N1) 2009 Virus Handling Human Remains • Transport of Deceased Persons with Pandemic (H1N1) 2009 Virus • Transport of deceased persons does not require any additional precautions when bodies have been secured in a transport bag • Hand hygiene should be performed after completing transport • Standard precautions should be used when handling deceased individuals, and preparing bodies for autopsy or transfer to mortuary services • Standard Precautions apply, and appropriate use of personal protective equipment (PPE) (e.g., gowns, gloves, masks, and/or eye protection) is recommended • After PPE is removed, hand hygiene should be performed 9/6/2009 505

Pandemic (H1N1) 2009 Virus Handling Human Remains Medical Examiner • Pandemic Influenza A(H1N1) 09 Virus handling of Human Remains 9/6/2009 506

Pandemic (H1N1) 2009 Virus Handling Human Remains Medical Examiner • According to HPSC autopsy should be undertaken in a premises complying with HBN 20 Facilities for mortuary and post-mortem services, NHS Estate – During autopsy procedures HCWs should wear the PPE advised for an aerosol generating procedure and comply with Health Services Advisory Committee, Safe working and the prevention of infection in the mortuary and post-mortem room, 2003 • Personal protective equipment (PPE) • Standard autopsy PPE, which includes: – Scrub suit worn under an impervious gown or apron – Goggles, face shield – Double surgical gloves with an interposed layer of cut-proof synthetic mesh gloves – Surgical mask or respirator – Shoe covers • Aerosols generated procedure: use of oscillating saws – FPP 2-3 disposable particulate respirators – Powered Air Purifying Respirator (PAPR) • Autopsy personnel who cannot wear a disposable particulate respirator because of facial hair or other fit limitations should wear a loose-fitting (e.g. helmeted or hooded) PAPR • Remove PPE before leaving the autopsy suite and dispose in accordance with facility policies and procedures 9/6/2009 507

Pandemic (H1N1) 2009 Virus Handling Human Remains Medical Examiner: Environmental Precautions for Autopsies • Autopsies on human remains infected Pandemic Influenza A(H1N1) 09 Virus in autopsy settings that have adequate air-handling system • Airborne infection isolation rooms (AIIRs): • Minimum of six (old construction) to twelve (new construction) air changes per hour (and direct exhaust of air to the outside or passed through a HEPA filter if air is recirculated • For autopsies, local airflow control (e.g., laminar flow systems) can be used to direct aerosols away from personnel; however, this safety feature does not eliminate the need for appropriate PPE • Use biosafety cabinets for the handling and examination of smaller specimens • Use vacuum shrouds for oscillating saws to contain aerosols and reduce the volume released into the ambient air environment 9/6/2009 508

Pandemic (H1N1) 2009 Virus Handling Human Remains Funeral Service • Pandemic Influenza A(H1N1) 09 Virus handling of Human Remains 9/6/2009 509

Pandemic (H1N1) 09 Virus Handling Human Remains Funeral Service • Pandemic (H1N1) 2009 Virus: • There should be minimal contact/handling of the body • When there is a need to do so, the following precautions are recommended: – When handling dead bodies, do not smoke, eat or drink and avoid contact with their own mouth, eyes or nose with their hands – Avoid direct contact with blood or body fluids from the dead body – Make sure that any cuts, wounds or abrasions are covered with waterproof bandages or dressings – Put on disposable gloves and protective clothing/uniform when handling dead bodies – Embalming is permitted – Gloves, surgical mask, apron and goggles should be worn by morticians – Viewing and touching of remains is permitted once skin cleansing/hygienic preparation is completed – Relatives who are worried about having already been exposed to the infection should contact the physician – Cremation is recommended for the deceased’s body 9/6/2009 510

Pandemic (H1N1) 2009 Virus Bioethics 1. Equity of access to antivirals and vaccines 2. Transparency, honesty and good Ethical Dilemmas in a Pandemic Proceedings of the Irish Council for communications Bioethics Conference 17th October 2006, Dublin 3. Individual autonomy v. public good  Freedom vs. Quarantine 4. Imperatives of urgency in outbreak Dr. Darina O’Flanagan situations 5. Duty of care of healthcare workers and value of reciprocity of employers 9/6/2009 511

Pandemic (H1N1) 2009 Virus Global Migration and Quarantine The WHO has no free-standing international quarantine authority “Quarantine” is still a country-by-country power! QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 512

Pandemic (H1N1) 2009 Virus Surveillance • A quarantine officer monitors passengers walking through a temperature screening checkpoint at Suvarnabhumi airport in Bangkok on April 24 Thermal Scanning 9/6/2009 513

Pandemic (H1N1) 2009 Virus Surveillance • Monitor ... a thermal camera monitors the body temperature of passengers to identify possible Influenza A(H1N1)vflu infections at Incheon International Airport, South Korea / AP 9/6/2009 514

Pandemic (H1N1) 2009 Virus Surveillance Around the World • A passenger goes through a disinfection process at the arrival terminal at the Juanda airport in Surabaya, in Indonesia's East Java province April 27, 2009 July, 12, 2009, thermal scanning in airports to decrease due to new mitigation policy strategy published from WHO! 9/6/2009 515

Pandemic (H1N1) 2009 Virus Travel Advisories 9/6/2009 516

Pandemic (H1N1) 2009 Virus Preventive Methods 1. Isolation Suspected swine flu patient (left) is escorted by a quarantine officer to 2. Quarantine Ambulance 3. Social Distancing 4. EU and Irish Quarantine Statue hard to find therefore US example Used! 5. In Ireland voluntary quarantine measures are presented in HPSC Post Exposure Prophylaxis “PEP” form QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 517

Pandemic (H1N1) 2009 Virus Preventive Methods • Definitions: • Isolation • The separation of an individual, or individuals, infected with a communicable disease from non infected individuals either in the home or hospital • Quarantine • The separation of an individual, or individuals, exposed to a communicable disease, from non infected and non-exposed individuals • Social distancing: • Refer to a range of non quarantined measures that might serve to reduce contact between persons, such as, closing of schools or prohibiting large gathering QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 518

Pandemic (H1N1) 2009 Virus New Definition of Quarantine • “Means the physical separation, including confinement or restriction of movement, of an individual or individuals who are present within an affected area, as defined herein, or who are known to have been exposed or may reasonably be suspected to have been exposed to a communicable disease of public health threat and who do not yet show signs or symptoms of infection with the communicable disease of public health threat in order to prevent or limit the transmission of the communicable disease of public health threat to other unexposed and uninfected individuals.” QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 519

Rationale for Isolation & Quarantine • Isolation is a fairly common infection control measure used to prevent the spread of disease to non-infected family, healthcare professionals, patients, etc. • Quarantine in an extreme public health Hong Kong Hotel Quarantined Due measure used to prevent the spread of to Swine Flu Case disease to the community 300 people at a Hong Kong hotel have been placed under quarantine after a guest there became China's first confirmed swine flu case. QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 520

When might Isolation & Quarantine be Considered? • Isolation is used primarily in health care facilities with highly infectious patients (e.g., varicella, measles, TB) • Quarantine is used in extreme circumstances when disease spread cannot be prevented by other means, such as by post-exposure prophylaxis (e.g. ,SARS)) • Quarantine is also used when exposed individuals refuse other disease prevention means, such as vaccination (e.g., smallpox) QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 521

Preconditions to Imposition of Quarantine or Isolation • Any quarantine or isolation is implemented in the least restrictive environment necessary to contain the communicable disease of public health threat • Any quarantined persons shall be confined separately from any isolated persons Metropark Hotel • Upon determining that any quarantined person Wanchai after a can be reasonably believed to have become Mexican traveller infected with a communicable disease of public was determined to health threat, the infected person shall be have the virus promptly removed from quarantine and placed in isolation QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 522

Preconditions to Imposition of Quarantine or Isolation • The health and disease status of any quarantined and isolated persons shall be monitored regularly to determine if such persons require continued quarantine or isolation • Any quarantined or isolated persons shall be immediately released from quarantine or isolation upon a determination that such quarantined or isolated persons pose no risk of transmitting the communicable disease of public health threat to other persons • The site of any quarantine or isolation shall be, to the extent practicable, safely and hygienically maintained with adequate food, clothing, health care, and other essential needs made available to the persons who are subject to any order of quarantine and isolation Movie media QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 523

Pandemic (H1N1) 2009 Virus Preventive Methods “Order of Quarantine” US Example • Ex parte-prepared by the Commissioner: • Sets forth: • Nature of the Public Health Threat including the specific disease if practical • Reasons why quarantine is required – Voluntary Compliance has failed or would be ineffective • Sufficient information to provide notice • Means by which the quarantine to be Biohazard implemented warning: • Geographic parameters (if any) This building • Duration of quarantine Under • Penalty for non-compliance Quarantine until • Provided to those covered individually if possible, further notice otherwise by a means determined by the Commissioner QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 524

Pandemic (H1N1) 2009 Virus Isolation “Order of Isolation” US Example • Order of Isolation • Ex parte-issued by the Commissioner • Sets forth: – Identity of isolated persons – Bases for the isolation – Specific communicable disease – Site of the isolation – Date and time when isolation commences – Any conditions of the isolation QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 525

Pandemic (H1N1) 2009 Virus International Quarantine • BEIJING, May 6 (Xinhua) -- Passengers quarantined in the Chinese mainland who took the same flight with a Mexican national later diagnosed with influenza A/H1N1 in Hong Kong will be out of quarantine on Thursday if they display no flu-like symptoms, China's Ministry of Health said Wednesday QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 526

Pandemic (H1N1) 2009 Virus Quarantine Airports • Quarantine Triage “Red” passenger could get escorted to restricted area RED (Terminal) • There will be a documentation, and a qualified medical expert about the situation and the upcoming procedures. QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 527

Pandemic (H1N1) 2009 International Quarantine Reporting • Potential Quarantine Database (THAD)(Canadian) • International Health Regulations • Border Health Initiatives • Security and Prosperity Partnership • Global Public Health Information Network (GPHIN) • Passive and Active Surveillance ICU of the Jinan Infectious Disease Hospital in Jinan,China QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 528

Pandemic (H1N1) 2009 Quarantine Ethics • Targeting versus stigmatizing • Care in all communications • Public health officials, clinicians & the community must combat fear, stigma and discrimination through health education and communication QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 529

Pandemic (H1N1) 2009 In-Shelter Isolation Biohazard warning: This House Has been self quarantined until further notice Please keep Clear by 20 feet QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 530

Pandemic (H1N1) 2009 Virus International Quarantine Recommendations • Quarantine is a net not a shield • Enhance communication strategies • Use traveller data to inform syndromic definitions • Create port risk assessment tool • Identify essential key partners for training – Border Services – Cruise Lines and Airlines – Cargo Ships • Establish International Quarantine Working Group QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER QUARANTINE DO NOT ENTER 9/6/2009 531

Public Health Management for Contacts of Probable or Confirmed Case of on a Aircraft (Update June 2 2009) 9/6/2009 532

Influenza has a 72% attack rate in exposed persons in a 4.5 hour plane flight Communicability is highest 1-2 days before to 4-5 days after onset REMEMBER – SOCIAL DISTANCING IS 6 FEET! 9/6/2009 533

Pandemic (H1N1) 2009 Management OF Passengers Or Crew Members With Symptoms Of Influenza • Minimize the number of personnel directly exposed to the ill person Separate the ill person (6 feet) from others as much as possible without compromising flight safety • Have the ill person wear a facemask, if it can be tolerated, to reduce the number of droplets coughed or sneezed into the air • If a facemask can not be tolerated, provide tissues and ask the ill person to cover his or her mouth and nose when coughing or sneezing along with a plastic bag for proper disposal of contaminated tissues • Gloves are not intended to replace proper hand hygiene. Gloves should be carefully removed and discarded and hands should be cleaned immediately following activities involving contact with body fluids. Gloves should not be washed or reused • Personnel having close contact with an ill person should wear a facemask at a minimum or, ideally, a NIOSH-certified particulate respirator rated N- 95 or better Leaflets warning passengers of possible • Dispose of soiled material, gloves, items contaminated with body fluids, and disposable respirators in a sturdy plastic bag that is tied shut and not swine flu symptoms reopened, and disposed of according to state solid waste regulations 9/6/2009 534

Pandemic (H1N1) 2009 Irish Port Health Travel Alert Resources • 29 April, 2009, notices were put in place at Irish ports and airports 9/6/2009 535

Pandemic (H1N1) 2009 Risk Travel Advisories • Department of Health and Children and Department of Foreign Affairs travel advisory Aug , 20, 2009 Chinese health workers in protective outfits examine passengers onboard an AeroMexico flight AM 98 that landed at Pudong international airport in Shanghai from Mexico Thursday, April 30, 2009 9/6/2009 536

Irish Embassy in México • Embassy • Ambassador His Excellency Dermot Brangan Travel Advisory • Address: First Secretary Security Status Embassy of Ireland Sarah Mangan May 18 2009 Secretary Cda. Blvd. Avila Camacho, 76-3 Myles Doherty Col. Lomas de Chapultepec Honorary Consulate 11000 Mexico D.F. • Address: Mexico Honorary Consulate of Ireland Telephone: Av. Coba 15 Mza.8 +52 55 5520 5803 SM22 Fax: Cancún Security Status 77500 Quintana Roo Aug , 20, 2009 + (52 55) 55 20 58 92 Telephone: Email: +52 998 112 5436 Submit your query here Fax: Website: +52 998 884 9940 www.irishembassy.com.mx Email: Exercise Caution consul@gruporoyale.com Honorary Consul: Anthony Leeman 9/6/2009 537

HPSC Travel Precautions • Travelling Precautions • Do not travel or fly home if you are ill • Familiarise yourself with sources of health • If you become ill during a flight you should advice in the country of travel, and pay inform the cabin crew attention to local government and public • Cover your nose and mouth with a tissue health announcements including any when coughing, sneezing or wiping and movement restrictions and prevention dispose of tissues into a bin immediately recommendations • If you are caring for someone who is ill, try to • Avoid close contact with people who have ensure they are not in close contact with fever, sneezing or cough others. Wearing a mask may be protective, • General advice includes frequent and for those who are caring for someone with thorough hand washing with soap and water, influenza or alcohol based hand cleaners • Clean surfaces regularly to get rid of germs • If you are sick, avoid close contact with others, stay at home or in your hotel room. • If you have a mild flu-like illness seek medical advice over the phone if practical • Seek medical care if severely ill 9/6/2009 538

Pandemic (H1N1) 2009 Advice for Travellers to Ireland Update 9/6/2009 539

Pandemic (H1N1) 2009 Passenger Health Questionnaire 9/6/2009 540

Pandemic (H1N1) 2009 Aircraft Cleaning Guidance 9/6/2009 541

Cabin Air Quality Risk of Contagious Viruses Suspected SARS Passenger coming WHO/ECDC has issued risk into Frankfurt assessments on cabin air Airport quality outlining to be vigilant due to documented transmissions on aircrafts! 9/6/2009 542

Pandemic (H1N1) 2009 Ship Cleaning Guidance 9/6/2009 543

Pandemic (H1N1) 2009 Irish Marine Notice May 8 2009 9/6/2009 544

Pandemic (H1N1) 2009 Virus Sydney Harbour Cruise Ship Quarantine? • The Pacific Dawn has already been blamed for a spike in Australian swine flu cases after authorities last week allowed 2,000 passengers to disembark in Sydney despite a suspected swine flu outbreak aboard • At least 46 passengers and crew aboard a previous Pacific Dawn cruise that docked at Sydney a week ago have been infected with the virus • June, 1, 2009 A cruise ship carrying three crew infected with swine flu agreed not to dock in northern Australia According to information received from SHIPSAN, there has been 12 cruise ships with influenza A(H1N1) cluster outbreaks since the beginning of the pandemic, the first one being reported on May 25, 2009 Pacific Dawn: Passengers line the upper deck of the P&O Cruises Pacific Dawn ship as it docks at Darling Harbour in Sydney 3 days later • Embarked to emergency medical teams testing for Influenza A(H1N1)! 9/6/2009 545

EU SHIPSAN TRAINET • EU SHIPSAN TRAINET project which started in 2008 and will be completed in May 2011 • This project foresees the development of: a) Harmonised communicable diseases surveillance including ILI syndrome by using standardised reporting forms b) A manual providing hygiene standards (e.g. for disinfection and cleaning), and outbreak management guidelines for airborne diseases c) Training of port health personnel and crew members on hygiene issues and outbreak management d) A communication network for collection and sharing of surveillance and ship inspection data among competent authorities • Eurosurveillance, Volume 14, Issue 21, 28 May 2009 • Perspectives • Preparedness for the prevention and control of influenza outbreaks on passenger ships in the EU: the SHIPSAN TRAINET project communication 9/6/2009 546

EU SHIPSAN • Current Country Totals From 24 Apr 2009 to 11 Aug 2009 Ireland (IE) 10 cruise ships have visited the ports of Ireland with no reports of Pandemic Influenza 9/6/2009 547

What are the differences between Pandemic (H1N1) 2009 Virus and the Seasonal influenza/Common Cold? General Indicators Pandemic A(H1N1) 2009 influenza Virus Seasonal Influenza Outbreaks Occurs rarely (three times in 20th century - last in 1968) Outbreaks follow predictable seasonal patterns; occurs annually, usually in winter, in temperate climates Immunity No previous exposure; little or no pre-existing immunity Usually some immunity built up from previous exposure Emergency response Health systems may be overwhelmed Health systems can usually meet public and patient needs Vaccine Vaccine probably would not be available in the early stages of a pandemic Vaccine developed based on known flu strains and available for annual flu season Non pharmaceutical Intervention May cause major impact on society (e.g. widespread restrictions on travel, Generally causes modest impact on society (e.g., some school closing, closings of schools and businesses, cancellation of large public gatherings) encouragement of people who are sick to stay home) Antivirals Effective antivirals may be in limited supply Adequate supplies of antivirals are usually available Econmy Potential for severe impact on domestic and world economy Manageable impact on domestic and world economy Symptoms Pandemic A(H1N1) 2009 Influenza Virus Common cold Onset Suddenly Slowly Fever Characteristically High (≥38oC or 100oF) Rare Headache Prominent Rare General aches and pain Usual, often severe Rare Fatigue, weakness Can be prolonged for a number of weeks Quite mild Extreme exhaustion Early and prominent Never Stuffy nose Sometimes Common Sneezing Sometimes Usual Sore throat Sometimes Common Chest discomfort, cough Common, can be severe Mild to moderate, hacking cough Diarrhoea, vomiting Commonly Not associated with the common cold in adults 9/6/2009 549

Seasonal Influenza Compared to Pandemic Proportions of Types of Cases Deaths Requiring hospitalisation Clinical Deaths Requiring symptoms hospitalisation Clinical symptoms Asymptomatic Asymptomatic Seasonal influenza Pandemic 550

Reactive and Proactive School Closures in Europe • ECDC: • 4 types of school closures: 1. School closure: – Closing a school and sending all the children and staff home 2. Class dismissal: – A school remains open with administrative staff but most children stay home 3. Reactive closure: – Closing a school when many children and/or staff are experiencing illness 4. Proactive closure: http://ecdc.europa.eu/en/files/pdf/Health – School closure or class dismissal before significant _topics/0906_TER_Public_Health_Measure s_for_Influenza_Pandemics.pdf transmission among the school children occurs Please refer to this document for technical assessment of school closures and As of Aug, 17, 2009 other public health measures the Irish Teachers Association met with the HSE and after consult it is recommended to keep schools open! 9/6/2009 551

Pandemic (H1N1) 2009 Influenza in Educational Institutions/Schools 9/6/2009 552

Pandemic (H1N1) 2009 Influenza At Irish Colleges • “Reactive” Temporary closures of 3 Co. Donegal colleges: 1. Colaiste Bhride in Ranafast is to close today and its remaining 275 students are being sent home 2. Coláiste Mhuire at Loughanure A swine flu notice for parents is closed after 11 confirmed cases of displayed at Colaiste Bhride, Ranafast, Co Donegal, as the the swine flu virus and a further school closes 140 students showed symptoms 3. Gael Linn course held in Magheraroarty closed and sent home 160 students home 9/6/2009 553

Pandemic (H1N1) 2009 Co Mayo , “St John's National School” • St John's National School in Breaffy near Castlebar, Co Mayo • 7 year old girl in first class has now been quarantined and is responding well to treatment at home • Transmission occurred from relative returning from abroad • Theses children meet Influenza A(H1N1) contact case definition and post- exposure prophylaxis protocol! • Therefore anti-viral medication will now be provided to 28 St John's National School in Breaffy children who were in the girl's class • The HSE said that the school remains open! Unless the Department of Public Health advises the school to close • Parents voluntarily have removed some children as a precautionary measure • All children will see there GP upon returning to school ! • Contact HPSC immediately upon probable or confirmed case in schools!  Influenza A(H1N1)virus has been identified at a National School in Co Roscommon. (July, 2, 2009) • Roxboro NS is a five-teacher school with more than 130 pupils 9/6/2009 554

Pandemic (H1N1) 2009 Irish School Recommendations • This virus currently appears to be acting like seasonal influenza in terms of the severity of illness and transmission of infection. Given this information, schools can remain open with appropriate isolation of the individuals at home or close school at their discretion, based on public health and community assessment • Other recommendations for schools are as follows: • Each morning, parents and caregivers should assess all family members and especially school-age children for influenza-like illness (defined above) • School staff should assess themselves for influenza-like illness • Students or staff with influenza-like illness should stay home and not attend school for at least 7 days even if their symptoms resolve sooner • If after 7 days, the student or staff continues to have acute symptoms, he or she should stay home until 24 hours after these symptoms resolve • Schools should observe students and staff for influenza-like illness at school • Students and staff who are ill should be removed from the classroom and sent home • If a student or staff is ill with other symptoms, they should stay home at least one day to observe how the illness develops • Students and staff with influenza-like illness should stay home and not go into the community unless they need medical care. Ill students should not attend extracurricular activities, community activities or child care Mekkah Stamps, 6, (left) and Mark • Environmental services should follow routine cleaning and disinfection procedures for Vazquez, 5, (right) prepare to serve all school buildings. No special cleaning or disinfection products are recommended. snacks while wearing protective gloves as a prevention against swine flu at Environmental services staff should use appropriate personal protective equipment Children's House daycare including gloves when using chemical cleaners or disinfectants • Childcare facilities should clean and sanitize frequently-touched surfaces, (such as desks, doorknobs, computer keyboards, toys) routinely and if they become visibly soiled Adapted from CDC School (K – 12) Dismissal and Childcare Facilities 9/6/2009 555

Pandemic (H1N1) 2009 Influenza Virus Irish School JI-6 th Year Check List Example 1.0 Mitigation and Actions Prevention: Completed In Progress Not Started  Create a committee to produce a plan for the preschool or child care program to deal with pandemic flu • The committee should include (if possible • Staff members • Representatives from the local school districts • Director of the program or preschool • Representative from the family child care organization • Parents/family members Completed In Progress Not Started  Assign staff to identify reliable sources of information; watch for public health warnings about flu, program closings, and other actions taken to prevent the spread of flu  Contact the local health department [find a list of local health officers at (Outside Source)] to learn who in your area has legal authority to close child care programs if there is a flu emergency  Review your facility’s disaster and mass casualty plan and determine if any changes need to be made to respond to pandemic flu.  Identify all the ways a flu pandemic might affect your program and develop a plan of action  Identify individual(s) in your program who will educate and supervise children, staff, and families about washing hands, following hygiene/cough etiquette, obtaining seasonal influenza vaccine, and staying home when sick  Develop and implement procedures for routinely sanitizing toys, furniture, and surface areas in your facility  Develop communication and dissemination plans for staff and families, including information about schedule changes, busing changes, and possible school or center closures  Encourage families to have a backup plan for finding care for their children if the program is closed during a flu pandemic or if their child is ill. Give them ideas about where they might seek help based on your knowledge of the local child care community L earn about services in your area that can help your staff, children, and their families deal with stress and other problems caused by a flu pandemic. Contact the local mental health department  Stage a tabletop drill with key staff members to test your plan and then improve it as needed. Repeat the drill from time to time. Consider volunteering to help in tests of community plans  Talk to other child care and preschool programs in your area to share information that could make your plan better. Discuss ways programs could work together to produce a stronger plan and pool resources  Anticipate the potential fear and anxiety of staff, children, and families due to rumors and misinformation, and plan communications accordingly. Consider developing key messages for various scenarios Not everything on this list will apply to every child care agency and preschool. This list will serve as a guide to child care agencies as they develop their own plans. It is important for all child care agencies to communicate with and know the rules and policies of local agencies, such as the local 9/6/2009 health department, local office of emergency services and education board. All of these agencies 556 will have important roles if there is a pandemic

Pandemic (H1N1) 2009 Influenza Virus Irish School JI-6th Year Check List 2.0 Preparedness: Actions Completed In Progress Not Started  Give staff and children’s families reliable information in their language and at their reading level on the issues listed below:: How to recognize a person who may have the flu and what to do if they think they have the flu How to care for ill family members  Teach staff, children, and their families how to limit the spread of infection by using good hand washing; covering the mouth when coughing or sneezing; and cleaning toys frequently  Educate staff and families about pandemic flu and the school plan. Explain why you need to have a plan. Give them a chance to ask questions  Plan how you would deal with program closings, staff absences, and gaps in learning that could occur during a flu pandemic  Plan ways to help families continue their child's learning if your child care program or preschool is closed  Plan ways to continue basic functions if your program is closed  Keep on hand a supply of surgical masks and several days’ supply of soap, paper towels, tissues, and cleaning products you will need to help control the spread of infection  Tell families that experts recommend yearly flu shots for all children six months to five years old and for anyone who cares for children in that age range  Encourage staff to get flu shots each year  Review procedures for communicating with staff, children, and families  Review the plan for identifying ill children and staff, isolating and masking them as necessary, and sending them home Identify or develop educational materials for families and staff on topics such as how to support their child(ren) with recovery from pandemic flu, common symptoms and constructive ways to cope with stress 9/6/2009 557

Pandemic (H1N1) 2009 Influenza Virus Irish School JI-6th Year Check List 3.0 Response: Actions Completed In Progress Not Started  Tell families to let your program know if their children are sick or when a family member is sick with accurate records of when children or staff are absent. Include a record of the kind of illness that caused the absence (e.g., diarrhea/vomiting, coughing/breathing problems, and rash)  Use a standard set of steps for checking children and adults each day as they arrive to see if they are sick. Make it clear that any child or adult who is ill will not be admitted  Have a plan for keeping children who become sick at your program away from other children, such as a fixed place for a sick room, until the family arrives. Masking affected children is also advisable  Require staff members to stay home if they think they might be sick. If they become sick while at the program, require them to go home and stay home  Require ill children to stay at home until their flu symptoms have gone and they feel ready to come back to your program  Hold staff meeting(s) to provide information on the extent of infection in your program and potential changes that may take place.  Conduct timely debriefings with the program pandemic committee to identify lessons learned and make necessary changes to the response plan 4.0 Recovery: Actions Completed In Progress Not Started  Hold staff meetings and provide information on the extent of pandemic flu in the community  Announce counseling support services that are available to staff. Utilize employee assistance programs for coping with loss and stress  Announce counseling support services that are available to children and families  Provide rest places for those staff and children who tire easily  Make educational materials available to families and staff on topics such as how to support their child with recovery from pandemic flu, common symptoms of loss and grief, and constructive ways to cope with stress  Identify children, families, and staff who may need long-term physical and mental health support or intervention, and refer them to community resources to provide these services  Monitor the effects of cumulative stress on caregivers  Consider offering health and mental health services, if available, by community university, or public/nonprofit mental health agencies, and identify funding to support these services  Modify work roles and responsibilities or consider adding volunteer or support staff as needed  Document “lessons learned” and incorporate them into revisions and training 9/6/2009 558

Public Health Management Pandemic (H1N1) 2009 Influenza Virus in Educational Institutions • Guidance for Departments of Public Health on the management of Pandemic (H1N1) 2009 in an educational institution (update 28th August 2009) http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHe althProfessionals/PublicHealth/Guidance/File,3820,en.pdf 9/6/2009 559

Public Health Management of Pandemic (H1N1) 2009 Influenza in Educational Institutions • Aug 28th Update Guidance for Departments of Public Health on the management of Pandemic (H1N1) 2009 in an educational institution • http://www.hpsc.ie/hpsc/AZ/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdviceforHealthProfessionals/PublicHealth/Gu idance/File,3820,en.pdf • Topics covered: • Frequently asked questions: Influenza A (H1N1)v (Swine Flu) information for parents • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3900,en.pdf • Frequently asked questions: Influenza A (H1N1)v (Swine Flu) information for educational institutions Pages 1-12 • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3725,en.pdf • Guidance for Third Level Institutions in preparing for Influenza A (H1N1)v. • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3822,en.pdf • Guidance for residential educational institutions in preparing for Influenza A (H1N1)v. • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3891,en.pdf • Guidance for Crèches/Preschool Settings in preparing for Influenza A (H1N1)v. • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3890,en.pdf • Frequently asked questions: Influenza A (H1N1) in Educational Institutions/Schools. Information for Educational Institutions. • http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/EducationalandChildcaresettings/File,3891,en.pdf 9/6/2009 560

Pandemic (H1N1) 2009 Irish School Resources • Schools can download useful posters and general information in various languages from these websites – www.swineflu.ie • Provides daily updates on the pandemic – www.dohc.ie • Provides posters and documentation for educational settings – www.hpsc.ie 9/6/2009 561

Pandemic (H1N1) 2009 Irish School Resources • All information can be downloaded from or hyperlinks • Department of Education's website on Pandemic (H1N1) 2009 influenza • The following two documents have been produced by the Department of Education and Science in consultation with the HSE 1. Information sheet for Schools, Colleges and Centres of Education on Influenza A(H1N1) - Last updated on 27th August 2009 2. Circular 47/2009 Sourcing Information on and responding to Pandemic (H1N1) 2009 within Primary and Post Primary Schools. • One Page fact sheets for Parents, Students and School Staff – How Students can Prevent the Spread of Pandemic (H1N1) 2009 (Swine Flu) at School – How Teachers and other School Staff can Prevent the Spread of Pandemic (H1N1) 2009 (Swine Flu) at School – Advice for Parents if school is closed or children are sick and must stay at home because of Pandemic (H1N1) 2009 (Swine Flu) – Advice for Parents of Children at high risk of complications of Pandemic (H1N1) 2009 (Swine Flu) – Advice for Parents of Children with special needs regarding Pandemic (H1N1) 2009 (Swine Flu). • Posters to promote hand hygiene and general awareness on the Pandemic – Suds up and away! - Childrens hand washing advice – Adult Handwashing Poster – Be A Germ-Buster - Wash Your Hands Poster – Help stop the flu from spreading! - HSE Flu Childrens Poster – Information for the Public on Influenza A(H1N1) Poster 9/6/2009 562

Pandemic (H1N1) 2009 Influenza Virus School Teaching Tools • Other Information for Children & Teachers – Henry the Hand video “Henry the Hand School Visit” – The Children's Page (USDA Food Safety & Inspection Service) – Germs on the Run! (USDA Food Safety & Inspection Service) – Colouring book #1 (USDA Food Safety & Inspection Service) – Colouring book #2 (USDA Food Safety & Inspection Service) – Gross...You Didn't Wash Your Hands? (MicrobeWorld) – The Scrub Club – Children's Pack • CDC pod casts Things You Can Do to Stay Away from the Flu – http://www2a.cdc.gov/podcasts/player.asp?f=11416 • Institut pasteur – http://www.hygiene-educ.com/en/home.htm Full downloadable teachers education matrix with experiments, teaching aids and tools (Excellent resource package for teachers) • HPA e-Bug – http://www.e-bug.eu/ebug/game/movies/e-Bug_Junior_Game.html • It contains teaching materials and lesson plans on swine flu and related issues as well as interactive educational games for children on basic hygiene topics • Sesame street – http://www.cdc.gov/sesame.html?s_cid=healthyHabits_001 Many more on the web! 9/6/2009 563

Recommendations Regarding Prevention and Management of ILI in Residential Summer Camps • Interim guidance to Public Health authorities regarding day camps and residential summer camps for the prevention and management of influenza-like illness (ILI) suspected to be due to Influenza A(H1N1)v Recommendations Actions regarding Rationale: Reports of illness among school aged children and transmission within the school setting have been noted. With similar age groups typically attending day camps, it is Prevention and possible that the risk of transmission of H1N1 flu virus in the day camp setting may be similar to that seen in the school setting. In residential camp settings the risk of transmission may Management of ILI be higher due to the increased proximity and prolonged contact among campers, staff and volunteers in residential summer camps Completed In Progress Not Started Education  Camp Nurse should organise pandemic education with organizers  Consider development and implementation of a training program for camp staff regarding communicable disease control including specific information on how to recognize and report possible cases of ILI.  Have relevant age appropriate educational materials and information for campers available. Screening  Passive and active screening (laminated poster are available from HSE upon request) To help prevent entry of H1N1 flu virus into the camp setting, consider advising all camp attendees, prior to the camp start date, of the following:  Individuals who have had ILI within 7 days prior to arrival will not be allowed to attend.  Individuals who have been a contact of a case of ILI within the 7 days prior to arrival may attend camp and will be monitored (either self monitoring or actively monitored, whichever is most appropriate for the situation) closely for symptoms of ILI.  Consider active screening of all newly arriving camp attendees by asking if they have had symptoms of ILI within the previous 7 days or have been in contact with someone who has had ILI within the previous 7 days.  Take a health history of each attendee and note underlying conditions that may place them at high risk for complications of influenza.  Enhanced screening for symptoms of ILI throughout the camp period is advised to ensure early detection of potential cases and intervention as appropriate. Completed In Progress Not Started  Protocols should be in place for the management of individuals with ILI, including such things as how monitoring and care will be managed (e.g. designate staff to care for ill persons and recommend they limit their interaction with well persons) and when medical evaluation of ill persons should be considered.  Individuals with severe illness and those at high risk for complications should seek medical advice and/or care.  It is recommended that individuals who develop ILI be separated from the general population until arrangements can be made for them to return home or, if that is not an option, until 7 days after onset of symptoms.  Please note, individuals who are at high risk of complications from influenza should not be designated as caregivers for ill individuals.  If individual rooms for persons with ILI are not available or feasible, consider cohorting ill individuals by placing those with ILI in a room, cabin or tent specifically for ill persons, with beds at least 2 meters apart and nearby washroom facilities separate from those used by the healthy population.  Individuals with ILI should only leave the isolation area for medical reasons or other necessities. Whenever a person with ILI leaves the isolation area, he/she should take measures such as coughing or sneezing into a disposable tissue or sleeve and wearing a face mask, if available, to avoid exposing others to the virus  Individuals with ILI/or not should be instructed in hand hygiene and respiratory etiquette (age appropriate games)  For additional information regarding care of individuals with ILI, please refer to How to look after someone at home with H1N1 flu virus http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdvicefortheGeneralPublic/File,3660,en.pdf “How can I prevent myself from catching Influenza” http://www.hpsc.ie/hpsc/A-Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/AdvicefortheGeneralPublic/File,3662,en.pdf 9/6/2009 564

HPSC Pandemic Checklist for Third Level Institutions HPSC Update Aug 13 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/Educat 9/6/2009 ionalandChildcaresettings/File,3822,en.pd 565

HPSC Pandemic Checklist for Third Level Institutions http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/Educat 9/6/2009 ionalandChildcaresettings/File,3822,en.pd 566

Maynooth University “Pandemic Preparedness” • As of July 24 2009 the “National University of Ireland Maynooth” published their Flu Contingency Plan ver. 2.2 • Highlights: • Who pandemic alert levels and Irish alert level roles and responsibilities integrated: into a pandemic guidance document outlining : • Contents – 1.0 Purpose / Scope Of Plan 2 – 2.0 Flu Pandemic Introduction 2 – 3.0 Foreseeable Risks To NUIM & St. Patricks College 3 – 4.0 Alert Levels 4 – 5.0 NUIM & SPCM Flu Pandemic Response Team 6 – 6.0 NUIM & SPCM Responses To National Alert Levels 7 – 7.0 Role Of Medical Centre 17 – 8.0 Role Of Student Residences 18 – Appendix 1. Critical Equipment / Materials Checklist 19 – Appendix 2. Critical University/SCPM Functions 20 – Appendix 3. Medical Centre Critical Response Equipment Proactive Pandemic 21 Preparedness Planning – Appendix 4. Response To Suspected Flu Case On Campus 2 – Policies and procedures will be developed from these guidelines in their full pandemic plan and hopefully evaluated by table top exercises and mock drills 9/6/2009 567

Pandemic (H1N1) 2009 Ambulatory Care Clinics • In elective ambulatory care clinics (e.g. physiotherapy clinics, Well Baby and Well Woman clinics, outpatient follow-up clinics), where patients present for appointments: • It is suggested that clinic visits for patients who are ill with ILI symptoms be deferred until they are well • This may be facilitated by reminder calls to patients to reschedule their appointments if they have ILI and by signage at the entrance to the clinic reminding patients to not attend clinic and to reschedule for when their symptoms have resolved • The Well Women Centre • 67, Pembroke Road,Ballsbridge, Dublin 4. Tuesday / Wednesday 10.00 am - 7.30 pm Monday / Thursday / Friday 8.00 am - 7.30 pm Saturdays 10.00 am - 4.00 pm Tel: (01) 660 9860 / 668 1108 / 6683714 Fax: (01) ) 660 3062 • info@wellwomancentre.ie 9/6/2009 568

Pandemic (H1N1) 2009 Virus HPSC On Personal Resources • Women who are Pregnant or Breastfeeding: http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicI nfluenza/SwineInfluenza/Adviceforthe GeneralPublic/File,3732,en.pdf 9/6/2009 569

Pandemic (H1N1) 2009 Virus Breastfeeding Mothers • The risk for Pandemic Influenza A(H1N1) 09 Virus transmission through breast milk is unknown – However, reports of viremia with seasonal influenza infection are rare • Suspected or confirmed ill mothers – Should continue breastfeeding and increase feeding frequency • Rational: – Infants who are not breastfeeding are particularly vulnerable to infection and hospitalization for severe respiratory illness • Mothers should wear a mask! • Mask not tolerated, have tissues available 9/6/2009 570

Pandemic (H1N1) 2009 Infection Control for Parents • Instruct parent and caretakers on how to protect their infant from the spread of germs that cause respiratory illnesses Pandemic Influenza A(H1N1) 09 Virus : • Wash adults’ and infants’ hands frequently with soap and water, especially after infants place their hands in their mouths • Keep infants and mothers as close together as possible and encourage early and frequent skin-to-skin contact between mothers and their infants • Limit sharing of toys and other items that have been in infants' mouths. Wash thoroughly with soap and water any items that have been in infants' mouths • Keep pacifiers (including the pacifier ring/handle) and other items out of adults' or other infants' mouths prior to giving to the infant • Practice cough and sneeze etiquette 9/6/2009 571

HSE and the National Hand Hygiene Campaign • As of Aug 27 2009 HSE has now met all but 1 benchmarking activities according to ECDC for the “National Hand Hygiene Campaign” • (Updates in red dots) . . . . . . . . 9/6/2009 572

Pandemic (H1N1) 2009 Virus HSE Mass Media Video Encourage children to use “wash it”" rather than “kill it” IDS = Hearing Impaired Catch it! Bin it! Kill it! English: http://www.hse.ie/eng/swineflu/ Irish: Tá an fógra le fáil as Gaelige freisin IDS: http://www.youtube.com/watch?v=1Q6DwhIn3xo 9/6/2009 573

Pandemic (H1N1) 2009 Personal Prevention HSE Leaflet http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInf 9/6/2009 luenza/AdvicefortheGeneralPublic/File,3916,en.pdf 574

Pandemic (H1N1) 2009 Personal Prevention • First and most important: wash your hands – Try to stay in good general health – Get plenty of sleep – Be physically active – Manage your stress – Drink plenty of fluids – Eat nutritious food • Try not touch surfaces that may be contaminated with the flu virus • Avoid close contact with people who have symptoms such as fever, sneezing, coughing or shivering or (Large gatherings i.e.. Oxegen festival) • There is no indication for using masks except when caring for someone who may have flu • Pay close attention to health alerts in the country in which you are travelling 9/6/2009 575

Personal Steps To Take If you Experience Flu-like Symptoms What should I do if I get the flu? • If you get sick with a flu-like illness phone the HSE automated Flu Information Line on Freephone 1800 94 11 00, available 24 hours a day. • Listen to the symptoms of flu and the advice on caring for someone at home • You can also get this information on www.swineflu.ie • Most people with flu will be able to recover at home within a few days without needing anti-viral medicine or medical care http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInflu enza/SwineInfluenza/AdvicefortheGeneral Public/File,3916,en.pdf 9/6/2009 576

Pandemic (H1N1) 2009 Personal Prevention • If you get sick: • Stay at home for seven days – avoid spreading infection to others • Avoid public transport • If you get sick with a flu-like illness phone the HSE automated Flu Information Line on Freephone 1800 94 11 00, available 24 hours a day. • Listen to the symptoms of flu and the advice on caring for someone at home • Use surgical mask if available • Cover your nose and mouth with disposable tissues when sneezing, coughing, wiping and blowing your nose • Dispose of used tissues in the nearest waste bin • Wash your hands often with soap and water, and especially after coughing and sneezing. Alcohol-based hand cleaners are appropriate • Anti-fever (Antipyretic) medication such as paracetamol or aspirin (NB aspirin should NOT be given to children under 16 years of age) • Drink plenty of fluids • Ensure that all household surfaces that are touched by hands are kept clean, especially doorknobs, light fittings, bedside tables, bathrooms and kitchens surfaces and children's toys – Such surfaces should be wiped regularly with a household disinfectant according to directions on the product label 9/6/2009 577

Pandemic (H1N1) 2009 Adult Emergency Warning Signs for Consult or Re-consult • In adults, emergency warning signs that need urgent medical attention include: • Difficulty breathing or shortness of breath • Coughing up bloody sputum • Pain or pressure in the chest or abdomen • Sudden dizziness • Drowsiness , disorientation or confusion • Severe or persistent vomiting • Fever for 4-5 days and not resolving or once feeling better and then developing a high fever If you have taken the basic care steps outlined above and you start to feel worse, or if after a few days you are not feeling better, you may need further advice from your doctor. Contact you doctor by phone or the FluInformation Line (Freephone 1800 94 11 00) 9/6/2009 578

Pandemic (H1N1) 2009 Children Emergency Warning Signs for Consult or Re-consult • In children emergency warning signs that need urgent medical attention include: • Fast breathing or trouble breathing • Bluish skin colour • Not drinking enough fluids • Not waking up or not interacting • Being so irritable that the child does not want to be held • Flu-like symptoms improve but then return with fever and worse cough • Fever with a rash 9/6/2009 579

Pandemic (H1N1) 2009 Virus Personal Prevention From Spreading the Virus Preventing the spread of Swine Influenza includes: • If you are sick, limit your contact with other people as much as possible • Do not go to work or school if ill • Cover your mouth and nose with a tissue when coughing or sneezing • I t may prevent those around you from getting sick • Put your used tissue in the waste basket • Cover your cough or sneeze if you do not have a tissue. Then, clean your hands, and do so every time you cough or sneeze 9/6/2009 580

Pandemic (H1N1) 2009 Personal Prevention From Spreading the Virus Cover your mouth and nose with a tissue when coughing or sneezing • No Tissue 9/6/2009 581

Pandemic (H1N1) 2009 Personal Prevention From Spreading the Virus • Washing your hands often will help protect you from germs • Wash with soap and water or clean with alcohol- based hand cleaner • We recommend that when you wash your hands -- with soap and warm water -- that you wash for 15 to 30 seconds, visibly soiled 60 seconds • When soap and water are not available, alcohol- based disposable hand wipes or gel sanitizers may be used • You can find them in most supermarkets and drugstores • If using gel, rub your hands until the gel is dry – The gel doesn't need water to work; the alcohol in it kills the germs on your hands 9/6/2009 582

Correct Hand-washing Protocol 1st step: 2nd step: 3rd step: Palm to palm Palm of right hand over Palm to palm with Attention: including back of left hand and palm fingers wrists (30 sec). of left hand over back of Interlaced(30 sec). right hand(30 sec). 4th step: 5th step: 6th step: Back of fingers to Rotational rubbing o fright Rotational rubbing, backwards opposing palms with thumb clasped in left palm and forwards with clasped fingers interlocked(30 and vice versa (30 sec). fingers of right hand in left sec). palm and vice versa (30 sec). 9/6/2009 583

Pandemic (H1N1) 2009 Personal Prevention From Spreading the Virus • Alcohol-based disposable hand wipes or gel sanitizers are encouraged 9/6/2009 584

Pandemic (H1N1) 2009 Personal Prevention From Spreading the Virus • Respiratory Etiquette/ Cough Etiquette Breaking the Chain of Infection 9/6/2009 585

Guidance For Caring For Persons At Home With Pandemic (H1N1) 2009 http://www.hpsc.ie/hpsc/A- Z/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/Advice 9/6/2009 forHealthProfessionals/GPs/File,3660,en.pdf 586

Many Countries Worldwide Are Committed To Improve Hand Hygiene You are part of a global movement! Countries committed in 2005, 2006, 2007 and 2008 Current status, March 2009 Countries planning to commit in 2009 9/6/2009 587

Pandemic (H1N1) 2009 Virus Business Continuity • An outbreak of swine flu dampened tentative hopes for the global economy, sending markets lower on Monday and analysts fear a possible pandemic could force countries further into recession. • The World Bank estimated in 2008 that a flu pandemic could cost $3 trillion and result in a nearly 5 percent drop in world gross domestic product, damaging prospects of recovery in a world economy deep in financial crisis. 9/6/2009 588

Pandemic (H1N1) 2009 Business Continuity • Excellent resource for Business Continuity Planning • Business Continuity Planning Checklist Responding to an Influenza Pandemic available inside! 9/6/2009 589

Pandemic (H1N1) 2009 Checklists • Hospital Pandemic Influenza Planning Checklist • Home Health Care Services Pandemic Influenza Planning Checklist • Health Insurer Pandemic Influenza Planning Checklist • Travel Industry Pandemic Influenza Planing Checklist • Business Pandemic Influenza Planning Checklist • Law Enforcement Pandemic influenza Planning checklist • Child Care AND Preschool Pandemic Influenza Planning Checklist • School District (K-12) Pandemic Influenza Planning Checklist • Colleges And Universities Pandemic Influenza Planning Checklist • State And Local Pandemic Influenza Planning Checklist • CDC website for download! • Excellent resources for comparing local, regional, and national plans 9/6/2009 590

Pandemic (H1N1) 2009 Virus Case ! Studies The purpose of these case studies is to give a better picture of the interrelationships of pandemic preparedness and mitigation efforts in foreseeing and managing an emerging pandemic on a local to global scale ! 9/6/2009 591

Pandemic (H1N1) 2009 Virus Case Studies Objectives • Review UK Planning Assumptions in Context to Pandemic (H1N1) 2009 (Sept 3 2009) • Review preliminary estimation of the reproduction ratio for new influenza A(H1N1) from the outbreak in México 9/6/2009 592

New Planning Assumptions in Context to Pandemic (H1N1) 2009 Planning assumptions to mid-May 2010: potential effects of A(H1N1) infection for the general population Available online: http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/doc uments/digitalasset/dh_104843.pdf

UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Planning assumptions to mid-May 2010: potential effects of A(H1N1) infection for the general population Clinical Attack Rate up to 30% of population nationally, up to 6.5% of population per week Peak Clinical Attack Rate locally, 4.5%-8% of population per week Case Complication Ratio up to 15% of clinical cases Case Hospitalisation Ratio up to 1% of clinical cases, of whom up to 25% could require intensive care at any given time Case Fatality Ratio up to 0.1% of clinical cases Peak Absence Rate up to 12% of workforce The graph below illustrates three possible profiles for local epidemics, one following the UK planning profile exactly and the others demonstrating possible local variations. Each has a total Clinical Attack Rate of 30% (represented by the area under each curve).

UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Planning Indicators Description: Assumption: Commentary: Clinical Attack Rate The proportion of the population In total, up to 30% of the population Commentary: (up to 30% of population) who become ill with influenza, may experience influenza-like-illness This is an average over all ages in the population. The final Clinical Attack Rate among totalled over the period covered. following infection with the A(H1N1) children under 16 may reach 50% during this period, with significantly lower rates than (These are the clinical cases.) strain within the planning period. 30% in older people (of the order of 15% in those over 65). All the above figures refer to people experiencing symptoms. The proportion of the population infected with the A(H1N1) virus (the serological attack rate) may finally be as high as 60%. This is because in addition to those who develop clinical symptoms, a similar number may be infected but show no or insignificant symptoms. Peak Clinical Attack Rate The proportion of the population • Nationally, up to 6.5% of the UK The maximum 8% figure for a local area is higher than the UK planning assumption of who become ill in the peak week. population may become ill with 6.5% because local outbreaks may not be synchronised. Indeed, if the UK epidemic is influenza in the peak week of the extended over a relatively long period, local epidemics may have peak Clinical Attack pandemic. Rates substantially higher than the UK epidemic as a whole. This is due to the UK • Up to 8% of the population in any epidemic curve being a composite of the local curves, which may vary in profile (see given locality may become ill with below), timing, and to some extent Clinical Attack Rate. As both highly-peaked and influenza per week in the peak week of more lengthy epidemics pose challenges, planning should take account of the full range a local epidemic. of possibilities. • These peak rates might be sustained for a fortnight. Case Complication Ratio The proportion of those ill with The complication ratio may be up to Complication rates appear to be higher, as a proportion of those who become ill, in the influenza who are expected to 15% of clinical cases (as defined above) children under 5, clinical at-risk groups and older people. Conversely, older people may require additional treatment, during the planning period. be less likely to become ill with this infection, but are more likely to suffer from such as the prescription of complications if they do become ill. antibiotics (but not necessarily hospitalisation, see below). Commentary for graph on next slide! Once again, these should be regarded as illustrative curves to aid planning, not predictions. Forecasting the timing of ‘Week 1’ of the UK epidemic is not possible at present. Because of the low numbers in early weeks as compared to “background” levels of influenza-like-illness, it will not be possible to tell whether ‘Week 1’ has been reached from case data alone (except in retrospect). However, a ‘reasonable worst case’ at present is that exponential growth in cases might resume when schools re-open (possibly augmented by effects of seasonality). In that case, ‘Week 1’ could be in early September. Based on the national profile shown, case numbers would then peak in mid to late October. It is also possible that the exponential growth could be more rapid than seen previously, leading to a peak at the start of October. However, ‘Week 1’ of the local epidemic curve may vary from local region to local region.

UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Local Planning Profiles: Proportion of Local Population Becoming Ill per week 9% UK Planning Proflie Percentage of Local Population 8% Local Planning Profile 7% Less Peaked Local Profile 6% 5% 4% 3% 2% 1% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Week number

UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Planning Indicators Description: Assumption: Commentary: Case Hospitalisation Ratio •the proportion of those ill with Up to 1% of clinical cases Whilst hospitalisation rates for seasonal influenza are typically in the range 0.5 - 1.0% influenza who (if capacity exists) during the planning of those who become ill, current experience in the UK with the A(H1N1) virus should be hospitalised, and period may require suggests that planning should continue on the basis of the assumption given above. • the proportion of those hospitalised hospitalisation. Of these, Similar comments apply to age groups as above for complications, except that there who would need intensive care (if up to 25% could require is some evidence of higher hospitalisation rates amongst children under 5. At capacity exists). intensive care at any given present, it is unclear whether this reflects relative severity of symptoms, or a more time. precautionary approach to hospitalisation. This is a priority area for further investigation, and any further information will be incorporated into planning assumptions when available. Case Fatality Ratio The proportion of those ill (clinical For A(H1N1) infections This may be regarded as precautionary in the light of what has been seen so far, but cases) who die due to influenza, during the planning the Case Fatality Ratio may increase in the autumn (e.g. due to a higher incidence of totalled over a complete outbreak of period, the eventual Case bacterial co-infection, viral evolution or host susceptibility factors). The figure of infection. Fatality Ratio (CFR) could 0.1% is therefore appropriate at present for planning purposes. be up to 0.1% of clinical Case Fatality Ratios are particularly difficult to estimate. To do so requires knowledge cases. of (a) the total number of cases, including those that are very mild, and (b) the number who die because of influenza but whose deaths have been recorded as due to an underlying condition made worse by influenza. Both these factors are difficult to ascertain. The delay between the onset of illness and report of death must also be taken into account when calculating this ratio. Simply comparing known cases with known fatalities at any given point in a pandemic can give a seriously misleading estimate of the CFR. To date, the evidence suggests that similar comments with regard to age groups apply as for complication rates. That is, the effects of differing Clinical Attack Rates and Case Fatality Ratios roughly cancel each other out. There is thus no marked difference between any age groups (including the under-5s) in the overall fatality rate due to this infection. To put the numbers in perspective, the combination of “reasonable worst case” 30% Clinical Attack Rate and 0.1% Case Fatality Ratio would result in a total number of deaths of about 20,000, or about 1/30th of the total expected each year from all causes (about 600,000).

UK Planning Assumptions in Context to Pandemic (H1N1) 2009 Planning Indicators Description: Assumption: Commentary: Peak Absence Rate The proportion of the workforce who may be Absence rates for illness may reach 12% This estimate refers to absence over and above that for “normal” holiday leave absent from work at the peak of the local epidemic of the workforce in the peak weeks of the and non-Swine Flu illness. because they are ill themselves or because they are planning period. The best current estimate of the length of illness is that: looking after ill children. • half those people becoming ill recover within about 7 calendar days • a further 25% need up to 10 calendar days to recover, and • 25% have symptoms for more than 10 calendar days. As an average (mean), the duration of illness is 9 calendar days. Current data, and analysis of previous pandemics, suggests an average unavailability for work of approximately 10 calendar days for clinical cases without complications, and 14 calendar days for those with complications. Based on analysis of previous pandemics, this includes some allowance for a short period of recuperation following recovery from clinical illness in addition to the period with flu symptoms. Also included in the assumption is an estimate for those at home caring for ill children, but not for any additional absence due to fear of contracting Swine Flu or the need to look after ill dependent relatives or friends other than children. If schools are closed due to influenza during term-time (due to lack of availability of staff or planned closure), absence rates may increase as parents may need to stay at home to look after children. It has been estimated that this could cause an additional 15% of the workforce to be absent for the duration of the school closure. This is based on the proportion of the national workforce with dependent children at home, as evidenced by survey data. This proportion will clearly differ from case to case, and employers should take account of the characteristics of their own workforce. These six slides and narrative commentary are cited and credited to Department of Health (DH) UK and are for review purposes only! Please see Hyperlink for reference!

Estimation of the Reproduction Ratio for influenza A(H1N1) from the Outbreak in Mexico “How do They do It” Boëlle PY, Bernillon P, Desenclos JC. A preliminary estimation of the reproduction ratio for new influenza A(H1N1) from the outbreak in Mexico, March-April 2009. Euro Surveill. 2009;14(19):pii=19205. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?Article Id=19205 Overview of Euro Surveillance Articles By Michael Fraser RN Of Irish First Point Responder Institute “Republic of Ireland” 9/6/2009 599

Pandemic Influenza A(H1N1) 09 Virus México Outbreak 2009 As of June, 26, 2009 Aguascalientes - 94 Hidalgo - 242 Morelos - 95 Querétaro - 141 Baja California - 79 Jalisco - 333 Nayarit - 73 Quintana Roo - 57 Baja California Sur - 8 San Luis Potosí - 372 As of June 24 Campeche- 38 2009 Sinaloa - 8 Laboratory Chiapas - 55 confirmed Sonora - 66 cases 8,279 Chihuahua - 58 Tabasco - 246 Deaths - 116 Tamaulipas - 68 Coahuila - 2 Tlaxcala - 69 Colima - 26 Veracruz - 321 Durango- 19 Federal District -1824 Nuevo León- 64 Yucatan - 97 Guanajuato - 79 Mexico State - 280 Oaxaca - 79 Guerrero - 214 Zacatecas - 237 Michoacán - 156 Puebla - 59 9/6/2009 600 Individual regions #’s are days behind

Influenza A(H1N1) México 9/6/2009 601

Influenza A(H1N1) México 9/6/2009 602

2009 Influenza A(H1N1) Outbreak in México (PAHO Epi Alert) Black=Deaths Red=Confirmed Cases 9/6/2009 603

Influenza A (H1N1) México Age Specific Attack Rate May 13 9/6/2009 604

México • Figure shows the number of confirmed (N = 97) and probable (N = 260)* cases of swine-origin influenza A (H1N1) virus (S-OIV) infection, by date of illness onset, in Mexico, during March 15 to April 26, 2009. • From March 15 through April 17, the daily number of confirmed and probable cases combined did not exceed five cases. However, the start of a substantial increase is indicated on April 18. This increase peaks at approximately 55 cases on April 22 and 23, before declining to fewer than 10 cases on April 26. 9/6/2009 605

Influenza A (H1N1) Summary of Age Specific Clinical Signs and Fatality Rate May 20 2009 9/6/2009 606

Influenza A (H1N1) México Age Specific Attack Rate May 20 9/6/2009 607

México's Age Specific Case Fatality Rate 9/6/2009 608

México Current Situation 9/6/2009 609

HPA Case Study Mexico's Hospitalization and Deaths 9/6/2009 610

Estimation of the Reproduction Ratio in México • Purpose: • Sustained human-to-human transmission is necessary to trigger influenza pandemic and estimating the reproduction ratio (average number of secondary cases per primary case) is necessary for forecasting the spread of infection and forecasting mitigation measures 9/6/2009 611

Estimation of the Reproduction Ratio In México • Two parameters must be estimated for this new virus using mathematical and computational models: 1. The reproduction ratio (R0) which measures the average number of secondary cases per primary case 2. The generation interval, which measures the average time between infection in a primary case and its secondary cases 9/6/2009 612

Estimation of the Reproduction Ratio for Influenza A (H1N1) Methods for Estimating R • Two different approaches were used to estimate R: • M1 - Intrinsic growth rate • M2 - Real time estimation 9/6/2009 613

Methods for Estimating Generation Interval Distribution • The two methods require full specification of the generation interval distribution • As no information regarding the actual generation interval in Mexico is available, they used three plausible candidate values of the generation interval (denoted GI) derived from different approaches: • 1. (denoted as PAN) obtained from household studies from the 1957 and 1968 pandemics • 2. Derived from viral excretion in experimental influenza infection (denoted as VIR) • 3. Hypothetical distribution introduced in Elveback (denoted ELV) 9/6/2009 614

Methods for Estimating Generation Interval Distribution • Their values with mean standard deviation (SD) were the following: • PAN = 3.1 +/- 1.9 days • VIR = 2.6 +/- 1 day • ELV = 4.6 +/- 1.5 days 9/6/2009 615

Estimation of the Reproduction Ratio for influenza A(H1N1) M1 - Intrinsic Growth Rate • When using M1, the period starting on 9 April and ending on 24 April yielded the best fit for exponential growth, with daily rate r = 0.30 [CI95% 0.28-0.34] 9/6/2009 616

Estimation of the Reproduction Ratio for Influenza A(H1N1) M2 - Real Time Estimation • With method M2: • Estimates of the daily reproduction ratio R(t) in the outbreak of new influenza A(H1N1) in Mexico, calculated with method M2 (see Methods) using three generation interval values: PAN GI (top), VIR GI (middle) and ELV GI 9/6/2009 617

Epidemic Growth Rates and Reproduction Ratio Estimates • Epidemic growth rates estimated for the new influenza A(H1N1) epidemic in Mexico and corresponding reproduction ratio estimates calculated with method M1 9/6/2009 618

Results and Conclusion • A comprehensive analysis of all available data has independently led to the range of – (R0) 1.4-1.6 • Early estimates show that the reproduction ratio in Mexico was in a range similar to that of past influenza pandemics of 1967-68 9/6/2009 619

Other Case Studies from the ECDC • Enhanced epidemiological surveillance of influenza A(H1N1)v in Italy – As of 7 July 2009, a total of 158 laboratory-confirmed cases of influenza A(H1N1)v were reported in Italy, from half of the 21 Italian regions. To date all cases have had symptoms consistent with seasonal influenza and no severe or fatal cases have been reported. An active surveillance of cases has been set up in Italy in order to undertake appropriate measures to slow down the spread of the new virus. This report describes the routine and enhanced surveillance currently ongoing in Italy. • http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19266 • Epidemiology and control of influenza A(H1N1)v in the Netherlands: the first 115 cases – Introductions of the new influenza A(H1N1) variant virus in the Netherlands led to enhanced surveillance and infection control. By 24 June 2009, 115 cases were reported, of whom 44% were indigenously acquired. Severity of disease is similar to reports elsewhere. Our point estimate of the effective reproductive number (Re) for the initial phase of the influenza A(H1N1)v epidemic in the Netherlands was below one. Given that the Re estimate is based on a small number of indigenous cases and a limited time period, it needs to be interpreted cautiously. • http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19267 • Preliminary descriptive epidemiology of a large school outbreak of influenza A(H1N1)v in the West Midlands, United Kingdom, May 2009 – This report describes the preliminary results from the investigation of a large school outbreak of influenza A(H1N1)v in Birmingham, United Kingdom in May 2009, when influenza A(H1N1)v was confirmed in 64 of 175 (36%) symptomatic pupils and members of staff. Initial findings in this study suggest that the symptoms were mild and similar to those of seasonal influenza, with an illness attack rate of nearly one third. • http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19264 • An outbreak of influenza A(H1N1)v in a boarding school in South East England, May-June 2009 – An outbreak of influenza A(H1N1)v was confirmed in May and June 2009 in a boarding school in South East England involving 102 symptomatic cases with influenza-like illness. Influenza A(H1N1)v infection was laboratory-confirmed by PCR in 62 pupils and one member of staff. Control measures were implemented as soon as a case was confirmed and included school closure, active case finding and treatment as well as post-exposure prophylaxis offered to the entire school population. Had the outbreak had been detected earlier, the school closed earlier and prophylaxis commenced after the initial cases were detected, we may have seen lower levels of transmission. • http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19263 • Outbreak of influenza A(H1N1)v without travel history in a school in the Toulouse district, France, June 2009 – In June 2009, for the first time in France, a confirmed outbreak of influenza A(H1N1)v without history of travel occurred in a secondary school in Toulouse district. A total of 15 cases were confirmed among students of which three were asymptomatic. This report describes the outbreak and its public health implications. • http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19265 9/6/2009 620

Pandemic System Model Coming soon! Performance Improvement in Preparing for Pandemics 9/6/2009 621

References See Narration! 9/6/2009 622

Influenza A (H1N1) Further information and References • Further information: • International http://www.hse.ie/eng/ • CDC, US http://www.dohc.ie • PHAC http://www.who.int/en http://www.cdc.gov/swineflu/ • PAHO http://ecdc.europa.eu/en/ • ECDC • http://www.nathnac.org/pro/swinefl • HPA, UK u.htm • WHO • Links • Irish • Health Service Executive (HSE) • Department of Health and Children • Department of Foreign Affairs • Department of Agriculture • Irish College of General Practitioners (ICGP) 9/6/2009 623

Disclaimer: • The opinions expressed by authors contributing to this PPT do not necessarily reflect the opinions of The Irish First Point Responder Institute or the Editorial team or the institutions with which the authors are affiliated. • Neither the Irish First Point Responder Institute nor any person acting on behalf of the IFPRI is responsible for the use which might be made of the information in this PPT. 9/6/2009 633

Congratulations on completing the presentation! If you like a copy of the presentation please contact : michaelfraser.ifpri@gmail.com The cost of the presentation is €10.99 (includes vat) “Irish First Point Responder Institute” accounts management office: Mailing address: Breda Fraser 65 Dara Court Celbridge, Co. Kildare “Republic of Ireland” Available in hard copy or e-mail attachment! 10% of cost will go to Local Charity 9/6/2009 634

The End of Pandemic Influenza A(H1N1) 09 Virus “The 2009 Pandemic” By Michael Fraser RN Of Irish First Point Responder Institute “Republic of Ireland” 9/6/2009 635

Pandemic (H1N1) 2009 Master Update Sept 6 2009

0 comments

Notes on slide 1

3 Favorites