Influenza Pandemic Plan

Strategy for Austria
English Translation of the 3rd Edition

Influenza Pandemic Plan
Strategy for Austria

Manual
English Translation of the 3rd Edition

Influenza Pandemic Plan

Forword
In January 2004 the appearance of influenza viruses which could impair the health of animals and ultimately, as a secondary effect, human beings, was confirmed by the World Health Organisation (WHO). This confirmation proves that the possibility that new aggressive influenza viruses will emerge in future has grown. In the past, the emergence of new influenza viruses was often only recognised after a massive increase in the number of influenza cases, but since January 2004, on the strength of epidemiological and virological research, it has been possible to clarify that the possibility of an influenza pandemic (that is a worldwide epidemic) is higher than it has ever been since 1968 – when the last influenza pandemic occurred. On account of this possibility, the WHO has called on all countries to prepare corresponding measures in case an influenza pandemic breaks out. The legal basis for the measures that could be taken to protect people in Austria should this happen is based on the Epidemic Law by which the federal authorities are assigned the coordinating tasks and the provincial authorities the operative execution. My ministry, together with national experts from the respective sciences and experts from the Austrian provinces has, during the past 18 months, worked out a plan entitled “The Influenza Pandemic Plan – Strategy for Austria”. The aim of the Influenza Pandemic Plan is to lay down a clear outline with clearly defined competencies so that, should the necessity arise, one will be able to react efficiently and without delay to the prevalent situation. The Influenza Pandemic Plan should be understood as a basic framework which contains the essentials of operative plans for a pandemic on the provincial level but is at the same time flexible enough so that it can be adjusted to the relevant concrete situation at any time. Besides written guidelines, information leaflets and background information, guidelines on influenza surveillance, on how to obtain medicine for prophylaxis and treatment, as also vaccines, and the measures which must be taken in hospitals are all laid down. The appearance of influenza viruses in human beings and animals is under constant observation by the relevant groups of experts at the international, European and national level. New scientific findings and information about the dispersion of these viruses will also constantly find their way into the Austrian preparation plans. Thus the present nationwide influenza pandemic guidelines and those which specifically adhere to the provinces will regularly be revised and brought up to date. These measures guarantee that the scientific and administrative aspects have been taken into account and that therefore the preconditions for optimal execution are given.

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Unlike many countries in the world, thanks to our economic prosperity and the excellent standard of our national health and communications systems, we are in the fortunate position of being able to offer the best preconditions to protect the Austrian population.

Dr Andrea Kdolsky Minister of Health, Family and Youth

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Contents
Forword................................................................................................... 5 1. Summary of procedures and measures ............................................. 10 1.1. WHO und EU ..................................................................................10 1.2. The pandemic crisis committee .........................................................10 1.3. Information and communication........................................................11 1.4. Cooperation with the veterinarian services .........................................11 1.5. Measures to be taken in case of a pandemic .......................................12 1.5.1. Regional cooperation .................................................................12 1.5.2. Maintenance of public services ....................................................12 1.5.3. Legal foundations ......................................................................12 1.5.4. Vaccination ..............................................................................12 1.5.5. Medicines .................................................................................13 1.5.6. Protective masks .......................................................................14 1.5.7. Hospital preparedness................................................................14 1.5.8. Ambulance services ...................................................................14 1.5.9. Surveillance..............................................................................15 1.5.10. Increasing vaccination coverage for seasonal influenza .................15 1.5.11. Further development of the pandemic plan..................................15 2. Competencies and measures of the health authorities ...................... 16 2.1. Competencies ................................................................................16 2.1.1. Phases (following the WHO)........................................................16 PHASE 1 ........................................................................................17 PHASE 2 ........................................................................................18 PHASE 3 ........................................................................................19 PHASE 4 ........................................................................................20 PHASE 5 ........................................................................................21 PHASE 6 ........................................................................................22 The pandemic reaches Austria ..........................................................23 End of first wave of pandemic ...........................................................24 Second or further pandemic waves ....................................................24 2.2. Measures to be taken by the health authorities ...................................25 2.2.1. Expansion and improvement of the existing epidemiological and laboratory diagnostic surveillance .........................................................25 2.2.2. Procuring stocks of prophylactic medicines....................................25 2.2.3. Contracts with vaccine manufacturers ..........................................26 2.2.4. Laying in stocks of masks ...........................................................26 2.2.5. Informing all those working in the health sector.............................26 2.2.6. Informing the population ............................................................27 2.2.7. Special measures of the health authorities ....................................27 3. Diagnostic ......................................................................................... 28 3.1. Clinical diagnosis of suspected cases .................................................28 3.2. Laboratory diagnosis .......................................................................28
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3.2.1. 3.2.2. 3.2.3. 3.2.4.

Diagnosis aims..........................................................................28 Samples...................................................................................28 Diagnostic methods ...................................................................29 Operative laboratories................................................................29

4. Hospital care and hygienic measures in hospitals ............................. 30 4.1. Hospital care ..................................................................................30 4.1.1. Admission of patients.................................................................30 4.1.2. Hospitalisations.........................................................................30 4.1.3. Treatment of secondary illnesses .................................................31 4.2. Hygienic measures in hospitals .........................................................31 5. Media and communication ................................................................. 34 5.1. The role of the media in risk perception .............................................34 5.2. Informing the population .................................................................34 5.3. Tactical measures ...........................................................................35 5.3.1. The interpandemic phase ...........................................................35 5.3.2. Pandemic .................................................................................35 5.4. Competencies ................................................................................35 6. Legal foundations .............................................................................. 37 6.1. Outline ..........................................................................................37 6.2. The obligation to notify the authorities...............................................37 6.3. Investigations - including investigations of contact persons...................37 6.4. Precautions against spreading the disease ..........................................38 6.4.1. Isolation ..................................................................................38 6.4.1.1. Obligation of hospitals to admit patients .................................38 6.4.2. Ambulance service ....................................................................38 6.4.3. Prescribing protective measures and preventive vaccination ............38 6.4.4. Epidemic doctors.......................................................................39 6.5. The task of the security forces ..........................................................39 6.6. Who may vaccinate? .......................................................................39 6.7. Liability .........................................................................................39 6.8. Use of a non-licensed vaccine ...........................................................40 6.9. Other measures (via the regional administrative authorities).................40 6.9.1. Measures against large crowds gathering......................................40 6.9.2. Prohibiting school and kindergarten attendance .............................40 6.9.3. Evacuating buildings, flats and houses etc. ...................................40 6.9.4. Traffic restrictions for the inhabitants of certains areas or for transport to the inhabitants of certain areas from outside ......................................40 6.10. Management of the dead bodies of influenza patients .........................40 Data for the Influenza Pandemic Plan ................................................... 41 1. Medical bases .................................................................................... 42 1.1. Clinical image.................................................................................42 1.2. Agents ..........................................................................................42 1.3. Prophylaxis and therapy ..................................................................42
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2. Epidemiology..................................................................................... 44 2.1. Epidemiology .................................................................................44 2.2. Vaccination coverage rates...............................................................48 3. Surveillance....................................................................................... 50 3.1. The national reference centre for influenza – epidemiology ...................50 3.2. National reference centre of influenza – laboratory ..............................51 4. Drugs ................................................................................................ 52 4.1. General information on effective influenza virostatics ...........................52 4.1.1. Amantadine..............................................................................52 4.1.2. Neuraminidase inhibitors ............................................................53 4.2 Prophylaxis/therapy with Oseltamivir/Tamiflu® (Roche) .........................54 4.2.1. Prophylaxis with Tamiflu®: ..........................................................54 4.2.2. Therapy ...................................................................................55 4.2.3. Dosage form.............................................................................56 4.3. Prophylaxis/therapy with Zanamivir/Relenza® (GSK)............................57 4.3.1. Prophylaxis with Relenza® : ........................................................58 4.3.2. Therapy with Relenza®:..............................................................58 4.3.3. Dosage forms ...........................................................................58 4.4. Accompanying therapy – antibiotics/NSAR..........................................59 5. Vaccines ............................................................................................ 60 5.1. Manufacture, documentation and licensing of a safe and effective vaccine60 5.1.1. Quality ....................................................................................61 5.1.1.1. Production .........................................................................61 5.1.1.1.1. The reference virus........................................................62 5.1.1.1.2. Possible use of gene technology ......................................62 5.1.2. Pre-clinical testing .....................................................................63 5.1.3. Clinical testing ..........................................................................63 5.1.4. Summary of product characteristics and package leaflet instructions for use ..............................................................................................63 5.2. Marketing authorisation procedure ....................................................63 SUPPLEMENT ......................................................................................... 65 Appendix 1: Explanatory leaflet – influenza – pandemic ..............................66 Appendix 2: Risk stratification for CAP (=Community Acquired Pneumonia) ...68 Appendix 3: Antibiotic therapy for CAP .....................................................69 Appendix 4: Sample sheet for hygiene file ................................................70 Appendix 5: Influenza – sentinella fax-registration form .............................71 Appendix 6: EU – influenza case definition ................................................72 Contributors .......................................................................................... 73 Addresses.............................................................................................. 74 Imprint.................................................................................................. 75

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1. Summary of procedures and measures
Pandemic plan set-up
• The pandemic plan consists of a o Frameworkplan by the Ministry of Health, Family and Youth (BMGFJ; MoH) which contains all the basic issues concerning the medical and legal foundations, diagnostics, epidemiology, surveillance, preventive methods and treatment, the composition of a crisis committee, hospital provision and hygienic and media issues, as also Provincial implementation concepts (operative plans) which contain concrete measures for vaccination, medicinal prophylaxis and hospital provision.

o

1.1. WHO und EU
• The WHO informs worldwide of an imminent pandemic and declares a pandemic. Via the EU’s Early Warning System, moreover, the Austrian MoH’s crisis committee is in constant contact with the “Health Threats Unit” of the EU’s DG Sanco and the European Centre for Diseases Prevention and Control (ECDC). This guarantees that the latest information from the crisis areas is immediately passed on while, on the other hand, EUwide coordinated action is possible (e.g. travel restriction, ban on flying, …).

1.2. The pandemic crisis committee
• Crisis committees have been set up both at the federal and provincial levels. They will be made up of the following: o A core team consisting of representatives of the board of directors of the Public Health Authorities including lawyers, reference centres, experts (epidemiology, virology, vaccinology..), vets and press delegates. Expanded crisis committee: representatives of the armed forces, the police, the ambulance services, the nursing services, health insurances, the chamber of pharmacists, NGOs,..

o

The members of the federal and provincial crisis committees must be on 24hour standby from Phase 5 onwards. An activation system via mobile phones that has been tested beforehand will guarantee that these crisis committees can meet within two hours. The MoH’s crisis committee and its contact persons are included in the Pandemic Plan. The provincial public health authorities will inform the BMGFJ as to who is in charge of their crisis
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committees. The federal and provincial crisis committees and the MoH can, if necessary, communicate via email or audio conferences in a crisis situation. The technical prerequisites for such communication will be secured in the interpandemic phase and tested as to their efficiency in the course of nationwide tests (e.g. Van Swieten, November 2006). • The MoH’s crisis committee will announce the relevant phases or levels based on the information it gets from the WHO or EU, and will coordinate the measures according to the phases or levels as laid down in the pandemic plan. This includes informing the population and the press. The crisis committee will also constantly keep the government informed.

1.3. Information and communication
• • The Ministry’s crisis committee will immediately pass on information from the WHO/EU to the provincial crisis committees. The population must be informed objectively and transparently. Clear information is essential and the crisis committees must agree on what wording is to be used. The MoH and the provincial crisis committees will prepare relevant material and pass it on to members of the press for use on the internet, at politicians’ press conferences, and for hotlines etc. A special media work group will continue to work on the present communications plan. Already in May 2006 a crisis communications plan with clear procedural directions and definitions of roles and responsibilities was completed. Meanwhile, moreover, approved phraseology and sample press announcements for the individual phases of a pandemic which can be used with slight adaptations have been prepared at EU level. At an informal meeting of EU ministers in February 2006, Austria emphasised the necessity of approved EU-wide press coordination in the event of a crisis in order to avoid alarming the population. The first measure of such an approved information policy has been to connect and network the press representatives of all the health ministries in the EU.

1.4. Cooperation with the veterinarian services
• In Austria, unlike in many other EU countries, the veterinarian services come under the MoH. In this way continuous coordination and cooperation is guaranteed. Besides briefings on topical issues, once a month a joint meeting of the pandemic crisis committee takes place to which all the ministries, the provincial representatives as also all important interest groups (as, for example, the Medical Association, the Association of Pharmacists, the National Health Insurance Associations..) are invited.

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An important aim of pandemic prophylaxis is to prevent avian flu from spreading to farm animals. Thus detailed instructions for poultry farmers to prevent poultry becoming infected, as also on how to cope with an outbreak of avian flu, were drawn up and sent to all poultry farmers. Prophylactic measures to prevent the staff themselves from becoming infected were naturally included.

1.5. Measures to be taken in case of a pandemic
1.5.1. Regional cooperation
• In March 2006, the first Regional Pandemic Meeting took place in Vienna to which all the neighbouring states were invited so that cross-border issues in the preparation for a pandemic (e.g. vaccine production, the closing of frontiers) could be discussed. In future, regional cooperation will be intensified.

1.5.2. Maintenance of public services
• All the state and regional public services (e.g. police, fire brigade, garbage collection, ambulance services etc…) were included in the stockage concept for key personnel and an adequate stock of neuraminidase inhibitors and facial masks procured. All private suppliers of public services (e.g. energy supplying companies,…) were supported in the precaution concepts and crisis plans that were drawn up in preparation for a pandemic. The State Crisis and Disaster Control Management Organisation (SKKM) is part of the Ministry for Inner Affairs. Its task is to coordinate measures in crises which affect the entire state. The SKKM will therefore take over coordination between the ministries, as also coordination between the Austrian Federal Republic and the provinces - which are primarily responsible for disaster control. The most important task here is maintenance of the infrastructure and public safety.

1.5.3. Legal foundations
• Quarantining of infected persons, protective measures for health sector employees or other endangered persons (vaccines, chemoprophylaxis), measures to stop mass gatherings, restricting traffic, deploying “epidemic specialists” and closing schools and kindergartens or other communal facilities are allowed under the Epidemic Law. It also allows the police and public safety organisations to take certain coercive measures.

1.5.4. Vaccination
• Vaccination is the least expensive and most effective protective measure against influenza. However, after the WHO laboratory network has identified

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the virus, there is lead time before the vaccine is available. The new “verocell” vaccine (= produced in tissue cultures) will be used, as the time it takes to produce, namely 10 weeks, is far shorter than for the the vaccine used up to now which was produced from chicken embryos (and took three months to produce). At the moment, moreover, this is the only way in which a large amount of vaccine can be produced at short notice. • It is imperative to vaccinate the entire population. In the early phase of production, not enough vaccine will be available, so priorities as far as supplies are concerned have been set. The aim of setting such priorities is to keep the morbidity and mortality rates of the Austrian population low and thus to maintain the infrastructure in working order: 1. Persons who run a higher risk of infection (e.g. medical and nursing personnel, …) 2. Persons who are essential for the maintenance of the infrastructure and of public safety (e.g. those responsible for food and water supplies, police, armed forces,…) 3. Persons who run a higher risk of complications (e.g. chronic heart or circulatory diseases,...) • The vaccine will be delivered to central depots in locations determined by the provinces. The provincial health authorities will develop a distribution concept for distribution of the vaccine within each province, as also a plan to carry out and document vaccination (e.g. vaccination by medical personnel at health centres, factories, schools etc.; vaccination campaigns carried out by the regional health authorities,…).

1.5.5. Medicines
• Antiviral drugs for the treatment of influenza will be available. Classical antibiotics will be used to treat the most frequent complications (e.g. pneumonia). Recommended antiviral drugs:

Influenza A and B: Oseltamivir (capsules, suspension) Zanamivir (powder to be inhaled): expansion of licensing procedures for prophylactic use in the final stages Only Influenza A: • Amantadine (tablets, sirup)

Antibiotics like macrolides, ketolides, amoxillin (+ clavulanic acid) are suitable for treating secondary illnesses. Information on up-to-date figures of antibiotic must be obtained from “Pharmig” (=The Association of Pharmaceutical Concerns) and from wholesalers. In case of shortages, the producers or “Pharmig” must be contacted and ways of procuring swift deliveries agreed on.

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1.5.6. Protective masks
• In order to avoid influenza infection, health care workers are advised to wear FFP3 protective respirators with exhalation valves when in direct contact with influenza patients. FFP3 respirators without exhalation valves are recommended for patients (see chapter on “Hygienic measures in hospitals”). Otherwise FFP1 or surgical masks should be used. If the national level does not use the whole amount of stockpiled masks the Federal States will receive a proportional part of these masks according to the population. The masks will be released together with the stocks of antivirals by the command of the MoH.

1.5.7. Hospital preparedness
• Influenza patients should be cared for at home or as out-patients for as long as possible. If no vaccine is available, contact persons should take neuraminidase inhibitors prophylactically. Analogous to SARS, each Austrian province will decide on at least one “influenza hospital” which will set up a crisis plan and a crisis committee during the interpandemic stage. All hospitals will prepare internal crisis plans. Each province will, moreover, draw up a provincial hospital crisis plan which will regulate cooperation between hospitals. A separate reception unit in which only vaccinated personnel will work must be set up for influenza patients. This is where the diagnosis, triage and if necessary admission to hospital will take place. In order to prevent influenza spreading within the hospital and to protect hospital personnel from infection, guidelines for hospital hygiene will be provided. The accustomed annual vaccination of hospital personnel against influenza should be continued.

1.5.8. Ambulance services
• • The reception unit of the hospital responsible is informed so that preparations can be made. The personnel escorting the patient keep to the guidelines defined for protection of personnel. In so far as his or her condition permits, the patient is provided with an FFP3 mask without a valve. The ambulance must be disinfected with a wipe down cleaning immediately after each transport.

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1.5.9. Surveillance
• • In cooperation with the influenza reference centres, the BMGFJ will build up one uniform Sentinella system by blending the two existing systems. The obligation to notify the authorities when human beings are infected with H5N1 and other avian flu viruses (suspected cases must of course also be reported) is already in force. The methods of influenza surveillance must be adapted to the infection rate in order not to overtax the laboratory capacity. In order to distinguish the pandemic virus from other viruses, diagnostic proof through laboratory test results is most important when the first patients are infected. This is the only way of proving that the pandemic has reached Austria and that all the measures of the pandemic plan come into force. Once the pandemic has spread within Austria, laboratory diagnosis will only be necessary in a few cases. In all other cases clinical diagnosis will suffice. The obligation to inform the authorities, however, must be strictly kept to in order to assess the size of the epidemic and adapt measures accordingly.

1.5.10. Increasing vaccination coverage for seasonal influenza
• Although the BMGFJ recommends vaccination against influenza for the whole population and especially for risk groups, vaccination coverage in Austria is only around 17%. In autumn 2006 a large scale advertising campaign was therefore undertaken in order to boost the vaccination coverage especially of hospital personnel.

1.5.11. Further development of the pandemic plan
• The manual on hand is continually updated with new developments and its operability checked. This will be undertaken by the BMGFJ in cooperation with the pandemic group and the work groups for pandemic preparation in the provinces. Important supplements will moreover be provided by the following: The subsidiary working group for health of the State Crisis and Disaster Control Management (SKKM), the working group Generic Preparedness Planning of the EU Health Security Committee, the ECDC as also the WHO influenza workshops.

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2. Competencies and measures of the health authorities
2.1. Competencies
Both the WHO and the EU have networks which continually monitor influenza activity and are also able quickly to inform the international community of states or EU members. In addition, both the WHO and the EU already have laid down framework concepts which must be adapted to the prevailing situation in each country. In order to delineate the compentencies in Austria, the following organisation of the interpandemic phase (phase 1-5) and of the pandemic have been settled on:

2.1.1. Phases (following the WHO)
Phase 1: No new subtype of the influenza virus to be found in humans The risk of humans beings infected by pathological influenza viruses circulating among animals is assessed to be slight even if they have already infected some human beings Phase 2: As above, but the pathological influenza viruses circulating do present a considerable danger that human beings will be infected Phase 3: Human infection through a new influenza virus subtype but no transmission from one human being to another (that is only exceedingly rarely when contact is very close) Phase 4: Limited human-human transmission – strictly confined locally Phase 5: Bigger human -human outbreaks – infection still confined locally Phase 6: Pandemic: increasing and constant spread of infection in the population The pandemic reaches Austria or countries bordering on Austria End of the first pandemic wave Second and further waves Post-pandemic period: End of pandemic Return to interpandemic period

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PHASE 1
No new influenzavirus subtype/-strain in humans formerly phase 0/level 0 BMFGJ • • • • • • Setting up of a national pandemic plan (completed) Nominating a crisis action committee (carried out) Standardising and optimating the early warning system (Sentinella-System) Provision of medicines/vaccinations (contracts with firms completed) Increasing vaccination coverage (negotiations with the main social insurance associations and employees partial subsidies (ongoing) Recommending seasonal influenza vaccination Provincial health authorities/provincial sanitary boards • • • • • Specific provincial detailed planning for the pandemic plan (completed) Nomination of a crisis action committee (completed) Contribution to epidemiological surveillance Distribution concept for neuraminidase inhibitors/vaccination concept including identification of key personnel (completed) Increasing vaccination coverage (recommendation of annual vaccination against influenza/the possibility of getting vaccinated at a health authority; recommendation of vaccination against pneumococcal pneumonia (ongoing) National reference centres • • • Epidemiological and laboratory diagnostic surveillance of influenza activity (ongoing) Optimising of an early warning system (ongoing) Cooperation with EISS (European Influenza Surveillance Scheme) Hospitals • Plans for increasing patient capacity (taking necessary isolation measures and possible shortage of personnel into consideration (ongoing)

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PHASE 2
Pathological influenza viruses in animals which pose a considerable risk for infection in human beings formerly also phase 0/level 0 BMFGJ • • • • • Cooperation with the WHO and the EU (exchange of information, coordination of acitivities) National handing on of information (federal ministeries, provincial authorities,…) Exercises in pandemic planning Continual adaptation of pandemic planning at the national level Media training Provincial health authorities/provincial sanitary boards • • • Passing on information within the province Contribution to epidemiological surveillance Continual adaptation of pandemic planning at the provincial level National reference centres • • Epidemiological and laboratory diagnostic surveillance (ongoing) Continual exchange with international laboratories Hospitals • • Keeping personal protection equipment for personnel at the ready Informing and training personnel The federal and provincial veterinary authorities • • Cooperation with the federal and provincial health authorities in the federal and provincial zoonose commission Should Austria be affected: measures according to the HPAI-Wild Bird-Avian Flu Regulations, the Animal Disease Act, the Avian Influenza and Newcastle Disease crisis plan and other pertinent legal regulations

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PHASE 3
New influenza virus subtype in humans but no human-human transmission (i.e. only very rarely when contact is particularly close) formerly phase 0/level 1 and 2 BMFGJ • • • • • • • • Cooperation with the WHO and the EU (exchange of information, coordination of activities) Nationwide passing on of information (federal ministries, provincial authorities,…) Pandemic simulation exercises Expert(groups) are devoted to evaluating the latest research data and experiences in the areas infected Continual adaptation of pandemic planning at the national level Preparation of information material for specifically oriented groups Media training Should Austria be affected: Informing the WHO, the EU, crisis committee goes into action Provincial health authorities/provincial sanitary boards • • • • • Passing on information within the province Contributing to epidemiological surveillance Exercises in pandemic planning Continual adaptation of pandemic planning at the provincial level If affected, informing the BMGFJ, provincial crisis committee goes into action District administrative authorities • If affected: epidemiological investigation and measures to prevent spreading National reference centres • • • Epidemiological and laboratory diagnostic surveillance Procuring reagents from international reference laboratories If affected: virological investigation Hospitals • • Continual adaptation of hospital disaster measures, simulation exercises If affected: isolation measures, use of protective equipment, OBLIGATION TO INFORM THE AUTHORITIES!

Federal and provincial veterinary authorities as in Phase 2

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PHASE 4
A new influenza virus subtype in humans, limited human-human transmission strictly confined locally formerly phase 0/level 3 BMFGJ • • • • • • Cooperation with the WHO and the EU (exchange of information, putting activities to the vote, informing about unusual events) Passing on information at the national level (federal ministries, provincial authorities,…) Current evaluation of pandemic planning on national level Activating the crisis committee (evaluation: current situation and experience) Activating of the crisis communication plan (information of the population: situation, travel advices, pandemic plan) Should Austria be affected: informing the WHO and the EU Provincial health authorities/provincial sanitary boards • • • • • • Passing on information within the province Contribution to epidemiological surveillance Current evaluation of pandemic planning on regional level Contribution to crisis communication Activation the crisis committee If affected: informing the BMGFJ, activating the provincial crisis committee District administrative authorities • If affected: epidemiological check and measures to prevent the spreading in cooperation with the provincial sanitary authorities National reference centres • • • Epidemiological and laboratory diagnostic surveillance (ongoing) Exchange with international reference laboratories If affected: virological check Hospitals/centres for acute medical care • If affected: isolation measures, protection equipment, OBLIGATION TO INFORM THE AUTHORITIES!

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PHASE 5
Bigger outbreaks but human-human transmission as yet limited formerly phase 0/level 3

BMFGJ • • • • • • • Cooperation with WHO, EU (exchange of information, co-ordination of measures, informing about unusual events) Passing on information at the national level (federal ministries, provinces,..) Activating the crisis committee (evaluation of current situation and experience) Updated information and guidelines for doctors and pharmacists Crisis communication: target orientated information (updated) Contacting vaccine manufacturers Should Austria be affected: informing the WHO and the EU; activating the national pandemic plan Provincial health authorities/provincial sanitary boards • • • • • • Passing on information within the province Contribution to epidemiological surveillance Contribution to crisis communication Activating the crisis committee Checking the distribution and vaccine concepts (priorities) If affected: informing the BMFGJ, activiating the provincial pandemic plan District administrative authorities • If affected: epidemiological check and measures to prevent spreading in cooperation with the provincial sanitary authorities National reference centres • • • Epidemiological and laboratory diagnostic surveillance (ongoing) Exchange with international reference laboratories If affected: virological check Hospitals/centres for acute medical care • • Check: disaster plans in hospitals/plans for taking in more patients If affected: isolation measures, protection equipment, OBLIGATION TO INFORM THE AUTHORITIES!

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PHASE 6
PANDEMIC Pandemic outside Austria (Europe) formerly phase 1 BMFGJ • • • • • • The crisis action committee in permanent session (evaluation of the situation and recommendation on how to proceed) Passing on information nationwide Informing the population: on the situation, travel recommendations, pandemic plan Updated information and guidelines for doctors and pharmacists Contacting vaccine manufacturers: securing early supply Activating the pandemic plan Provincial health authorities/provincial sanitary boards • • • • • Passing on information within the province (hospitals, doctors, pharmacists, ambulance services,…) Contribution to epidemiological surveillance Supporting the information policy of the BMGFJ Checking/activating the provincial pandemic plans Preparation for speedy, targeted application of the pandemic vaccine/preparation for the distribution and delivery of neuraminidase inhibitors for prophylactic use National reference centres • • Continuation of epidemiological and laboratory diagnostic surveillance Speedy processing and distribution of data to the health authorities Vaccine manufacturers • Producing a vaccine based on the pandemic strain Pharmed Austria • National marketing authorisation/approval of pandemic vaccine Hospitals/centres for acute medical care (including emergency services for doctors) • Checking: hospital disaster plans/plans for increasing patient capacity, availability of personnel, availability of protective clothing

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The pandemic reaches Austria
(or countries bordering on Austria) formerly phase 2 BMFGJ • • The crisis action committee and experts on permanent duty -> based on their recommendation: Execution of national pandemic plan as follow: o Release of stocks of neuraminidase inhibitors for prophylactic use o Assuring that Austria is supplied with pandemic vaccine o Passing on information at the national level o Informing the population (on the actual situation, symptoms, transmission rate, instructions on preventive behaviour o Graded prophylaxis – primary target groups for prevention with neuraminidase inhibitors/vaccination o Guidelines for doctors/pharmacists (prophylaxis, use of usual seasonal vaccine, criteria for hospitalisation…) o Commencement of mandatory reporting for pandemic influenza Provincial health authorities/provincial sanitary boards • • Activation of provincial pandemic plans (if not yet activated) Passing on information within the province (practitioners, medical emergency services, hospitals, ambulance services, pharmacists, schools, undertakers, cemetery administrators,…) Organisation of the distribution and delivery of neuraminidase inhibitors Organisation/execution of nationwide influenza vaccination with the pandemic vaccine beginning with the target groups Informing the population in cooperation with the BMGFJ Federal health office and Pharmed Austria • Nationwide release of the pandemic vaccine if not yet carried out National reference centres • Epidemiological and laboratory diagnostic surveillance National insurance authorities • Taking over the costs of treatment with neuraminidase inhibitors Hospitals/centres for acute medical care (including emergency services for doctors) • • • Activating hospital disaster plans Organising vaccination against influenza or prophylaxis with neuraminidase inhibitors for personnel Provision for increasing patient capacity

• • •

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End of first wave of pandemic
formerly phase 3 BMFGJ • • Declaring the end of the first pandemic wave Continuation of the general vaccination against influenza (depending on the availability of the vaccine) with special reference to the danger of further pandemic waves Adapting the nationwide pandemic plan according to the insights won during the 1st pandemic wave Provincial health authorities/provincial sanitary boards • Adapting the provincial pandemic plans according to the insights won at the 1st pandemic wave National reference centres • Drawing up a report on the pandemic in consultation with the BMGFJ and the provincial health authorities

Second or further pandemic waves
formerly phase 4 Procedure as in Phase 2 taking the existing supply of vaccine into consideration and the modification according to the insights gained during the first pandemic wave.

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2.2. Measures to be taken by the health authorities
New and hitherto unknown virus infections in humans keep emerging. There are two particular factors to note in cases of infection with new influenza virus subtypes/sub-strains: • • Effective, approved drugs for therapy and prophylaxis already exist, and one can reckon with the fact that within approximately ten weeks of the virus strain reaching the WHO for vaccine production first supplies will be available.

In order actually to make use of these of two particular factors in order to protect the population in a pandemic, the health authorities must make special plans in the following fields:

2.2.1. Expansion and improvement of the existing epidemiological and laboratory diagnostic surveillance
• Specific measures to prevent the spread of infection can only be taken if (new) influenza viruses in Austria are recognised as soon as possible and if at the same time the morbidity rate of the population can be approximately estimated.

2.2.2. Procuring stocks of prophylactic medicines
• As it is highly probably that sufficient vaccine will not yet be available by the time the pandemic reaches Austria, in the interim period, one will have to fall back on medical prophylaxis. During a pandemic, however, the worldwide demand for neuraminidase inhibitors suitable for prophylaxis cannot be met with average production. In Austria as in most EU countries stocks in accordance with the stock concept were therefore acquired. The amount of neuraminidase inhibitors in stock is sufficient to maintain the area-wide infrastructure of public life and the basic supply in Austria with particular consideration of the maintenance of health care. In the event, these stocks could also be used to protect particularly endangered persons. Vaccination can be extended to a greater percentage of the population by way of a phased plan depending on the danger and epidemiological parameter. Neuraminidase inhibitors should be stockpiled at a few central depots from which they will be distributed to supply centres at locations agreed on beforehand. In this way distribution from a central and secure depot to the consumer can take place according to a detailed logistical plan. The mainstay of this logistic will be provided by the army. In order to achieve the greatest flexibility possible and optimal overall achievement with the best possible use of the means at hand, the following drugs were purchased: Tamiflu® and Relenza® in the original packaging and Oseltamivir in bulk. The plans for distribution were drawn up at the federal level. Detailed plans were drawn up at the provincial level supplementary to the detailed plans for a pandemic in each province. They guarantee consumer supply for the core
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groups taking local conditions and the phased plans which orient themselves to the given epidemiological situation into consideration. Regulating access and preventing improper use are included in the logistic concept.

2.2.3. Contracts with vaccine manufacturers
• On account of the expected discrepancy between vaccine supply and demand, a contract with a vaccine manufacturer has been signed which guarantees that Austria will be supplied with vaccine from the very beginning. Until a sufficient supply of vaccine is available, analogous priorities and phased plans as with medical prophylaxis apply. As far as the distribution is concerned, tested channels via wholesalers which have already been used in other vaccine campaigns can be used. Surveillance by the provincial health authorities is advisable if quotas are used. The existing vaccination centres at municipal authorities, hospitals, schools, factories and national health centres should all be involved in carrying out vaccination. In order to guarantee the swift and well-aimed administration of the vaccine, federal logistics must be supplemented by the detailed implementation plans that will be worked out at the provincial level.

2.2.4. Laying in stocks of masks
• Protective masks contribute towards reducing the risk of infection. A simple OP mask can protect against the airborne infectious germs which infected persons exhale. FFP1-, FFP2- or FFP3-masks, depending on how effective their filters are, are risk-graded protective measures against inhaling airborne pathogens. The advantage of these masks is that they can be used on a large scale und are effective regardless of pathogen types, development of resistance and individual drug incompatibilities. All the authorities concerned have therefore purchased considerable stocks of suitable masks geared to their specific use. In addition, as part of the comprehensive concept which is intended to provide protective measures for the entire population according to the degree of danger people are exposed to, masks will be made available at wholesale chains to allow the population to purchase stocks of this simple and reasonably cheap prophylactic measure. (BMGFJ mask sale November 2006). With respect to the necessary protection of personnel when treating patients who have influenza, see the chapter on “Hygienic Measures in Hospitals”.

2.2.5. Informing all those working in the health sector
• Already in the interpandemic phase, doctors and health care institutions will be informed of the contents of the pandemic plan, in order to allow the hospitals for their part to co-ordinate the necessary detailed plans with the pandemic plan.
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Influenza Pandemic Plan

In a pandemic those working in the health care sector will need additional updated information on the epidemiological situation. Uniform federal guidelines for the prophylactic use of neuraminidase inhibitors, the use of the pandemic vaccine and possibly remaining supplies of seasonal influenza vaccines as also taking into consideration hospitalisation criteria etc. guarantee optimal use of all available resources.

2.2.6. Informing the population
• • Already today continual efforts are being made to inform the population on the implications of influenza and the prudence of yearly vaccination against it. In an influenza pandemic the BMGFJ will actively contact the media so that the population is informed as objectively and comprehensively as possible about the illness itself, the possibilities of infection, the current epidemiological situation and the phased procedure concerning prophylactic measures. Recommendations for practical ways of behaving both for healthy and sick persons will be broadcast. In addition, information will be provided on the BMGFJ homepage and a nationwide hotline established. The provincial health authorities support this active information policy and will supplement it with the specific situation in their provinces.

• •

2.2.7. Special measures of the health authorities
• Under the law for epidemics, infection with avian flu viruses must be reported. In addition, influenza can be made notifiable at any time under this law. The obligation to notify the authorities makes it possible to introduce special measures such as forbidding public gatherings which would result in larger numbers of people flocking together and of closing schools. The decision to introduce such measures regionally depends on various parameters like how infectious the virus is and how many people have contracted it in the region. The fatality rate and the available prophylactic and therapeutic resources also play a role in weighing up the situation. Applying the Epidemics Law also makes it possible to prescribe protective measures/protective vaccines for medical personnel, or in the individual case for other endangered persons. For detailed citation of all suitable legal measures that can be used see Chapter 6.

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Influenza Pandemic Plan

3. Diagnostic
3.1. Clinical diagnosis of suspected cases
Characteristic symptoms of influenza virus infections: • Sudden onset of fever • Headache • Extreme fatigue • Dry cough • Red throat • Congested nose • Muscle pain

3.2. Laboratory diagnosis
The most important task of laboratory diagnosis is to monitor influenza activity by investigation of samples which doctors and specific Sentinella doctors have collected from patients with a suspected diagnosis of influenza from all over Austria (and the confirmation/exclusion of those influenza cases). From seasonal influenza waves, it is known that once the wave of influenza has fully broken out, clinical diagnosis and laboratory diagnosis correlates in 80-85%. During this period there is therefore no need for individual diagnoses. It would only delay the beginning of treatment. The quick testing methods commercially available at the moment are relatively insensitive and lead to wrong negative results especially as far as older persons are concerned. During a pandemic, samples should be sent on to the Virology Institute which will act as a reference centre for monitoring circulating virus strains.

3.2.1. Diagnosis aims
• • • Early recording of virus activity in Austria. Swift identification of virus strains in circulation so that the effectiveness of the available seasonal vaccines can be made clear as soon as possible. Monitoring influenza outbreaks, recording new virus strains and stem mutations.

3.2.2. Samples
For direct virus proof: • Nasopharyngeal smear • Sucked off nasopharyngeal secretion (from babies and infants) • Bronchial secretion • Broncho-alveolar lavage

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Procuring biopsy and section material of samples: if possible within 72 hours of the first symptoms

In order to prove virus specific antibodies: • Serum • Whole blood Sample transport will either be carried out via a special transport system or per post keeping to the postal authorities’ guidelines (see guidelines 93/88/EWG).

3.2.3. Diagnostic methods
For direct virus proof: • Proof of virus specific proteins and nucleic acid sequences by means of immune fluorescence technology, ELISA and PCR directly in the samples • Cultivation of viruses from the sample material For proof of virus specific antibodies: • Complement fixation reaction • Hemagglutination-inhibition test

3.2.4. Operative laboratories
• Laboratory surveillance of influenza activity in Austria: o The Virology Institute at Vienna University, WHO reference laboratory for influenza diagnostic in Austria: Virus cultivation from sample material of suspected cases of influenza within the framework of the nationwide influenza surveillance (Sentinella system) Typing and subtyping of cultivated influenza virus stems; serological fine typing, characterisation of hemagglutinate and neuraminidase through PCR and sequence analysis Close cooperation with the WHO influenza centre Information from the public health authorities on start of the influenza season Laboratory diagnostic coverage of suspected influenza cases that have been clinically diagnosed outside the Sentinella system: o In the Vienna area: Virological Institute of the Vienna University Medical School o In the Graz area: Institute for Hygiene of the Graz University Medical School o In the Innsbruck area: Institute for Hygiene of the Innsbruck University Medical School o In the Linz area: Institute for Hygiene, Microbiology and Tropical Medicine at the Elizabethinen Hospital in Linz

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4. Hospital care and hygienic measures in hospitals
4.1. Hospital care
4.1.1. Admission of patients
In principle, extramural, that is out-patient care is desirable. Certain prerequisites for this are, however, necessary. There must be no complications during the course of the disease and the health care system, either through those living with the patient or through the health services, must function. For hospitalisation the following nationwide uniform triage criteria have been laid down as a guideline: 1. Medical indication: patient suffering from • Suspected pneumonia and o Vital parameters* (blood pressure, pulse, respiratory rate, state of consciousness etc) or o Chronic heart-circulatory/lung disease or immunodeficiency: e.g. immunosuppressive disease, oncological illness, COPD,… in addition particular indications: • Patient is a clear case of rhabdomyolysis/myoglobinuria, danger of acute renal failure • Patient suffers from myocarditis/pericarditis • Patient suffers from encephalitis, myelitis, Guillaine-Barré syndrome 2. Social indication: • Competent care at home not guaranteed or • In case of acute deterioration, transportation distance too far, i.e. more than a four-hour journey

4.1.2. Hospitalisations
According to model calculations, at an estimated morbidity rate of 30% without therapy, one can reckon with a total of 36 000 hospitalisations. Neuraminidase therapy would probably reduce the number of hospitalisation cases to 15 000. With an average hospital stay of 10-12 days the number of hospital beds required rises. In this case, 8 900 additional beds would therefore be required.
*UNSTABLE PARAMETERS • Impaired consciousness • Blood pressure – must be judged according to age, but systolic • values <90mmHg or a reduction >40mmHg of the patient’s starting value/normal value would be “unstable”. • Equally a MAP (mean arterial pressure) <60–70mmHg • Oxygen saturation

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Influenza Pandemic Plan
• • • <92% indoors in patients with otherwise “healthy lungs” Lower values can be tolerated in COPD- patients Shock

The following possibilities of recruiting “influenza beds” should be used: • Discontinuing elective admission • Using “class” beds to increase the number of beds discharging patients who do not need intensive care and can be looked after at home by the health services or by relatives • Using beds in military sanitary institutions in so far as they are not needed by the armed forces, as also at health resorts, private clinics and rehabilitation centres

4.1.3. Treatment of secondary illnesses
The following antibiotics1 are suitable for treating bacterial secondary illnesses: • Pneumonia: cerfuroxim (as a substitute curocef, p.o.zinnat). For details of risk strategy and risk groups see supplement 2-3 • Bacterial superinfection in general: macrolides, ketolides, amoxillin (+ clavulanic acid)2 and cefalexin
1

2

Expert opinion on CAP (CAP = Community Acquired Pneumonia), 14.11.02; chair: Univ-Prof Dr F. Thalhammer, Prim Dr N Vetter, in: CliniCum, special edition 10/2003; guidelines of the Paul-EhrlichSociety and the European Respiratory Society; expert communication (Univ-Prof DDr W. Graninger, OA Dr A. Lechner) Acc. Univ-Prof DDr W. Graninger in Austria Amoxicillin only also possible

4.2. Hygienic measures in hospitals
Agents The agent is an up to now unknown influenza virus in humans, against which neither human beings nor animals have developed natural immunity. Source of infection It is to be expected that the human pathogenic influenza virus can only be transmitted from one human being to another, even if primarily a new type of influenza virus can partly be transmitted from animals to human beings. Transmission course Direct transmission through airborne infection plays by far the greatest role as far as influenza viruses are concerned. Transmission through hands and objects cannot be excluded, as influenza viruses can survive for several hours outside the body especially in low temperatures and when humidity is low. Infectious substance Repiratory secretion Duration of contagiousness Up to now, as far as the known influenza viruses in humans are concerned: 3-5 days after the outbreak of the disease for adults and up to 7 days for children. In immunosuppressed patients virus secretion can last longer.

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Incubation period 1-3 days Symptoms (see materials for the pandemic plan – medical basis) Dealing with patients suspected of having influenza in medical institutions Patients with acute respiratory symptoms have to be isolated already in the outpatient area from other patients. Dealing with influenza patients in hospitals Patients suspected of having influenza or have been diagnosed with an influenza infection who have to be hospitalised, should be put in single rooms with their own bathroom unit and toilet or in rooms in a separate ward with common sanitary facilities (cohort isolation). Patients with a confirmed influenza infection and patients suspected of having influenza must not be isolated together. Similarly, contact persons without symptoms may not be put in with patients with a confirmed influenza infection or with patients suspected of having influenza. Transport of patients Patients with a confirmed influenza infection or suspected of having influenza may only leave the isolation area if this is urgently necessary. In such a case they must wear masks over their mouths and noses, preferably FFP2 masks without exhalation valves. If this is not possible, they should wear surgical masks. For the accompanying personnel the following personal protection measures are valid. Personal protection As long as the personnel is not reliably protected by vaccination, the following measures are necessary for every contact with patients with a confirmed influenza infection or who are suspected of having influenza: • Protective masks (nose and mouth protected) - the mask must fit tightly o FFP2 masks with exhalation valve for normal work at the bedside and in the out-patients o FFP3 masks with exhalation valve for aerosol producing measures Eye protection everywhere where FFP2 or FFP3 masks have to be worn Protective clothing (disposable smock with long sleeves and cuffs, disposable overall, protective suit ventilated from outside only for aerosol producing measures Disposable gloves which cover the cuff Hygienic disinfection of hands with an alcoholic disinfectant after taking off the gloves and the mask as also after contact with possibly contaminated surfaces (all the products for hygienic hand disinfection listed in the experts list are suitable)

• • • •

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Protective measures also apply to persons cleaning and disinfecting patient rooms. In a pandemic all persons in medical institutions who have contact with patients, even if there is no concrete suspicion of influenza infection, must wear multilayered mouth/nose masks as used on operation wards as a basic protection measure. Patients’ bedding and clothing The bedding and clothing of patients with a confirmed influenza infection or are suspected of having been infected with influenza, must be put into plastic bags, sealed and taken away. Surface disinfection All surfaces which patients who have a confirmed influenza infection or are suspected of having been infected or come into contact with influenza infections must be regularly disinfected and, within the framework of a final disinfection, must undergo a wipe-down decontamination. All disinfectants listed in the experts directory of the ÖGHMP (Austrian Society for Hygiene, Microbiology and Preventive Medicine) may be used. Beds Matress covers that can be wiped clean with disinfectant must be used. Patients’ crockery and cutlery If there are only a few patients, disposable crockery and cutlery is preferable. If the medical institution has an approved thermal disinfection dishwasher then this can be used for the crockery and cutlery used by patients with a confirmed influenza infection or who are suspected of having an influenza infection. The crockery and cutlery must be taken to the dishwasher in closed containers which must be disinfected after use. Personnel who put the crockery and cutlery into the dishwasher must wear disposable gloves. Medical equipment Medical equipment like stethoscopes and blood pressure gauges must be kept in the room and disinfected daily in an appropriate manner during the course of the final disinfection. Equipment which has been in contact with infected patients and which has had to be disposed of must undergo a thorough wipe-down disinfection and then appropriate sterilisation. Waste disposal Waste, particularly the tissues used by patients with confirmed influenza infection and patients suspected of having an influenza infection, must be put into plastic bags, sealed and taken away.

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5. Media and communication
5.1. The role of the media in risk perception
Appropriate information is usually necessary for a health hazard to be detected. The aim is to provide people with the information they need to make decisions on how to deal with risks in health or environmental matters. Risk communication has been defined as “the exchange of information on the type of risk, the extent of the risk, the significance and acceptability of the risk, and of risk management”. How the media report on a risk is by no means insignificant. Risk perception is stronger if the risk is perceived by the media. This is particularly so when new risks are reported and can have a strong formative influence. Reports in the media, above all sensational ones, can understandably confuse and frighten people and can veil scientific facts. Distorted reports of this kind can lead to misunderstandings.

5.2. Informing the population
(following the Swiss pandemic-plan) It is a case of fulfilling the demands for objective information and openness in dealing with the effects of a pandemic. The aim is to motivate the population to follow instructions and recommendations. Information should above all • • Contain facts on the significance of the disease, details on the spread of the virus and the extent of the epidemic Describe the problems and bottlenecks which can occur during vaccine production and distribution, and particularly explain the reasons for the introduction of priorities as far as the distribution of the vaccine and of antiviral drugs are concerned Describe the possibilities and limits of self treatment Contain recommendations on how to behave in a given situation Inform people on the advantages and possible risks of vaccination Describe the therapeutic measures for cases with complications

• • • •

The information will be prepared and released by the pandemic crisis committee. Care should be taken to anticipate possible questions and provide answers beforehand and not to sound high-handed. The information should be comprehensive and honest. The pandemic plan proceeds from the assumption that qualified and objective information will avoid panic in the population.

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5.3. Tactical measures
5.3.1. The interpandemic phase
• • • • • • • • Continuous information of the population and of medical personnel Increasing awareness of and preparation for the pandemic Information for companies concerning making provisions for a pandemic Information for and cooperation with the responsible authorities Promoting exchange of information with existing organisations like, for example, Disaster Aid, Red Cross etc Seminar for selected representatives of the press Electing official press agency spokespersons and/or the pandemic crisis committee Preparing a homepage

5.3.2. Pandemic
• • • • • • • • Key opinion leaders briefed daily by the crisis action committee Producing leaflets for the population which are in accordance with the current situation, information on the precautionary measures and way to behave Differently worded texts for lay people, medical personnel, pharmacists, authorities, companies, hospitals etc. Preparing texts for the press in accordance with the current situation Daily news reports and communiqués to the press Telephone and email conferences Coordination with ORF (Austrian Broadcasting Company) Setting up a hotline, daily briefing of hotline personnel if necessary

5.4. Competencies
During the preparatory stage, the provinces will keep in contact with the local press. The BMGFJ will do the same at the national level. In the case of a pandemic, the BMGFJ will publish national statements which will then be modified regionally. The distribution of information material will first and foremost be the job of the provinces. Updated communiqués for the media and for the population will be published daily should the pandemic have reached Austria. It would be advisable to appoint a BMGFJ media spokes-person to cope with media work and equally one for each province. After consultation, it will be their job to comment on the current situation and to answer questions. Interpandemic period Phase 1 and 2 • • Continuously informing the press Increased reporting shortly before and during the influenza season pointing to the threat of a pandemic
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• •

Possible sources of information: newspapers, journals (medical journals, lay journals), internet, TV and radio Installing a “Pandemic Homepage”

Pandemic warning period Phases 3 and 4 • • • • • • • • • Regular checking of WHO updates Activating the BMGFJ press working group Involving the BMGFJ press spokes-person Continuously informing the press Increased reporting shortly before and during the influenza season pointing to the threat of a pandemic Press conferences Compiling and updating texts for the media Keeping the homepage up to date Preparing a hotline

Phase 5 • • • • More frequent checking of WHO updates Stepping up media reports Preparing the first leaflets for the population Installing a hotline and advertising it (via radio, teletext TV news and special broadcasts)

Pandemic period Phase 6 • • • • Daily checking of WHO updates by the crisis action committee Preparing texts for the media Hotline Keeping the homepage up to date o o o o Activating the pandemic plan Meeting of the pandemic crisis committee which draws up a first report for the media Daily checking of WHO updates Producing leaflets with instructions on how to behave, information about vaccination, drugs and various protective measures, adaptation to current situation if necessary Daily media reports on the current situation, the pandemic crisis committee continuously informs media Advertising the hotline Declaring the end of the first wave Preparing the population for a possible second wave via the media

o o o o

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6. Legal foundations
With the regulation under the Epidemic Law on notifiable diseases of January 2006, the obligation to notify the authorities of infections with the A/H5N1 influenza strain and other avian influenza viruses was introduced. This regulation can now be found in § 1 of the Epidemic Law itself (amendment BGBI. I Nr.114/2006 idgF).

6.1. Outline
• • • • Epidemic Law 1950, BGBI. Nr.186/1950 idgF Regulation concerning corpses of people with notifiable diseases or suspected of having had such diseases, BGBI. Nr.199/1957 idgF Federal Food, Drug and Cosmetic Act, BGBI. Nr. 185/1984 idgF Professional law for health workers

6.2. The obligation to notify the authorities
(§§ 2 to 3 of the Epidemic Law) This was introduced for every suspected, infected and fatal case of human infection with the A/H5N1 influenza virus and other avian influenza viruses. If necessary, the obligation to notify the authorities can be expanded by regulation to include influenza in general. • • • Every patient who has the disease (that is, in whom the disease has been confirmed) Every death Every suspected case (all persons with symptoms which give rise to the suspicion that they have the disease)

6.3. Investigations - including investigations of contact persons
(§ 5 Epidemic Law) The regional administrative authorities (administrative authority for the district, in towns with their own statute the municipal council) must safeguard all the necessary investigations and surveys via the doctors in the public medical corps. The type and scale of the necessary measures will depend on the professional facts (e.g. the type and danger of the agent) and the number of infected patients. Infected persons, persons suspected of having the disease and those suspected of carrying the disease* are obliged to: • provide full information • undergo the necessary medical examinations (including laboratory tests etc)

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*Persons who show no signs of the disease but whose microbiological tests show that they are carriers, or who have been exposed to the disease in such a way that they can be assumed to be carrying it and could therefore pass it on.

6.4. Precautions against spreading the disease
(§§ 6 to 26 of the Epidemic Law)

6.4.1. Isolation
Isolation arrangements will be laid down when the time comes in the form of a regulation according to necessity based on professional opinion. 6.4.1.1. Obligation of hospitals to admit patients • Public hospitals are not allowed to turn away a person who has been committed to hospital by an administrative authority (such persons are to be regarded as unrefusable) and hospitals are obliged to keep such a person in hospital for the duration of the regulation (§22, §4 and §24 KAKuG) Furthermore, public hospitals are obliged to take in cases which require immediate hospitalisation (even without an order!) o If the person’s life is in danger or o There is a danger that the person’s health will otherwise be seriously damaged (=unrefusability)

Three provinces have regulations in their hospital laws on emergency hospitals (provisional expropriation of buildings for hospital purposes in war, elemental force or accidents).

6.4.2. Ambulance service
The transport of an influenza patient may only be carried out by trained and vaccinated personnel. Provision must be made for ambulances to be disinfected after each transport.

6.4.3. Prescribing protective measures and preventive vaccination
The district administrative authorities can prescribe protective measures (a.o. preventive vaccination). • For persons who professionally treat and care for the sick or manage dead bodies and for midwives (§17, §3 of the Epidemic Law) • For public health officers and personnel who carry out protective vaccinations Prescribing protective measures/preventive vaccination is furthermore possible for certain individual endangered persons (e.g. who have had contact with an infected person or a person suspected of having been infected). Protective measures CANNOT generally be prescribed for the entire population.

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6.4.4. Epidemic doctors
If there are not enough public health officers to fight the pandemic, the district administrative authorities can nominate epidemic doctors who will have the same authority as public health officers.

6.5. The task of the security forces
According to §§6, 7, 15, 17, 22 and 24 (measures to prevent the disease spreading, isolation, measures to prevent large crowds gathering, putting certain people under surveillance, vacating housing and restricting traffic for the inhabitants of certain villages or towns), the health authorities can ask the public security forces to support them in their tasks by using coercive measures. If a person commits an offense under §178 of the penal code (StGB) (“whosoever performs an act which may even minimally spread a notifiable, contagious disease among humans”) (The person concerned is aware of his or her condition and can infect others by his or her behaviour), or if, in connection with this, it is a case of a dangerous attack according to §16 Security Forces Law (SPG), then in the concrete individual case public security organs have the power to avert the danger, that is the power to act according to the provisions of the code of criminal procedure (StPO).

6.6. Who may vaccinate?
• • • Doctors who are entitled to practise their profession independently Interns (guidance and supervision – not topview) Senior nurses §15, §5 (individual cases on doctor’s orders, if they have been specially trained)

N.B. Medical students doing practical work in a clinic may NOT vaccinate! (§41, §5 Medical Law – concluding list).

6.7. Liability
• • • • For correct and comprehensive information – vaccinating doctors For carrying out vaccinations (including careful examination of contraindications – vaccinating doctors) For adverse effects of vaccination – no liability on the part of the state at the moment (as not cited in the relevant regulation of the law concerning the adverse effect of vaccination). Could quickly be taken up if the need arises For the vaccine (production according to state-of-the-art in science and apposite norms - “Good manufacturing practice” GMP) – the manufacturing firm

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6.8. Use of a non-licensed vaccine
This is possible within the framework of §12 of the Federal Drug Act if there is a reason for it.

6.9. Other measures (via the regional administrative authorities)
6.9.1. Measures against large crowds gathering
(§15 Epidemic Law) A • • • general prohibition or depending on how dangerous the situation is Limited to particular cases Limited to a particular period of time Limited to a particular area

6.9.2. Prohibiting school and kindergarten attendance
(§9 Epidemic Law) • • • Closing schools and kindergartens Informing the school authorities who must immediately carry out the closures Forbidding those suspected of being infected to attend schools or kindergartens etc.

6.9.3. Evacuating buildings, flats and houses etc.
(§22 Epidemic Law) Alternative housing must be provided if required.

6.9.4. Traffic restrictions for the inhabitants of certains areas or for transport to the inhabitants of certain areas from outside
(§ 18 Epidemic Law) • • Closure of schools, kindergartens etc. Informing a school authority which has to close schools immediately

6.10. Management of the dead bodies of influenza patients
The usual regulations for the sanitary police force apply.

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Data for the Influenza Pandemic Plan

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Influenza Pandemic Plan

1. Medical bases
1.1. Clinical image
Influenza in humans is caused by types A and B of the influenza virus. In the winter months, this disease occurs regularly in epidemic form and in typical cases is usually characterised by the sudden onset of a high temperature, headache, a sore throat, muscle pain, fatigue, rhinitis and a dry cough. The acute stage lasts about a week, the cough and the fatigue, however, last several weeks. In some people influenza can lead to serious complications, whereby, pneumonia - caused either by the virus itself or by bacterial superinfection – takes precedence. The risk for such complications is much higher among elderly people (>65) and people with other primary diseases, and consequently the annual influenza epidemics have a significant excess mortality.

1.2. Agents
A characteristic hallmark of the influenza virus is that it is subject to frequent mutations whereby above all the two antigenes on the surface of the virus, hemagglutinin (HA) and neuraminidase (NA) are affected. Continuous mutations are called an antigenic drift and occur both in influenza A and influenza B viruses. This antigenic drift is the reason why influenza virus infections do not result in lasting immunity and therefore why re-infections and annual epidemics can reoccur. Sudden and drastic mutations, known as an antigenic shift, are, however, a hallmark of the influenza A virus and turn up at unforeseeable intervals. If such drastically altered variations of a virus jump directly from one human being to another, extensive epidemics can occur and can therefore, as a further consequence, lead to a pandemic. A pandemic virus of this kind has occurred three times up to now in the recorded history of influenza and a new variant of hemagglutinine or neuraminidase has emerged each time. The worst pandemic, known as “Spanish Flu”, was caused by a subtype of the virus H1N1 in the years 1918/19 which costed 20 to 40m people their lives. The other two pandemics, in the years 1957 (“Hong Kong Influenza”) and 1968 (“Asian Influenza”), were caused by subtypes of virus H2N2 or H3N2.

1.3. Prophylaxis and therapy
(see also chapters 4 and 5) Prophylactic vaccination is an important measure to control influenza. At the moment, influenza vaccines contain two A strains and one B strain which are selected from the virus strains currently circulating. The effectiveness of the influenza vaccine depends primarily on the age and immune competency of the vaccinated person as also on the similarity of the antigens contained in the
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vaccine with the actual viruses in circulation. Optimally, in healthy persons under 65, the influenza vaccine can prevent infection in 70%-90% of cases. In older persons the effectiveness is only 30%-70%. Various drugs are available both for specific therapies as also for prophylaxis. Amantadine and Rimantadine are only effective against Influenza A viruses, while the newer neuraminidase inhibitors (Zanamivir and Tamiflu®) cover the Influenza B virus. If taken within the first 48 hours after onset of the infection, both groups of drugs have proved effective in reducing the intensity and duration of the symptoms, and if used prophylactically prevent infection in more than 70% of cases. The conditions for the emergence of new human pathogenic influenza viruses of epidemic potential are given in nature, and occurrences of influenza in the form of pandemics must therefore also be reckoned with in the future. As history shows, such pandemics can definitely assume catastrophic proportions and effect entire populations and the social structure of whole countries. In such a situation, it can be assumed that massive bottlenecks in the supply of vaccines and antiviral drug products will occur internationally. The organisation of an appropriate stock of drugs or ensuring supplies is therefore an important measure to keep morbidity and mortality rates low in the event of a pandemic.

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2. Epidemiology
In Austria approximately 380 000 people per annum contract influenza, roughly 4 500 of whom have to be hospitalised. Thus, although influenza is among the most frequent and serious infectious diseases, risk awareness in the population is inadequate. This is evident from the dramatically low vaccination coverage of an average 17% which, despite intensive efforts to inform the population, has only risen very slowly.

2.1. Epidemiology
The epidemiological depiction of an infectious disease is generally possible on the basis of: • • • The data of a nationwide surveillance system Data on hospital discharges with diagnostic classification according to ICD (=International Classification of Diseases) Sentinella data

Even if influenza is a notifiable disease in many EU countries, influenza activity is usually depicted on the basis of sentinella data because sentinella systems have proved to be a better method of surveillance. Thus the data is reported weekly and according to a clear case definition by a small number of highly motivated Sentinella doctors who cover a defined catchment area. The reference centre analyses the data immediately and thus influenza activity can be monitored in “real time”. While nationwide data is also collected by means of the classical reporting system, the quality is often bad and the data not up-to-date. The reason for this is that under the Epidemic Law the doctors who report influenza data have at the same time to report a multitude of contagious diseases and the benefits of the extra time spent on this bureaucratic exercise is not directly apparent to them. Hospital discharge and mortality data are additionally evaluated in order to acquire data on hospitalisation and deaths caused by influenza. At the moment influenza is not a notifiable disease in Austria as the BMGFJ is of the opinion that it would not improve influenza surveillance. The current Sentinella system is to be expanded, however, and installed nationwide. The following data sources were used to depict influenza epidemiology in Austria: the sentinella data from the period between 1992 and 2001 was projected (1) and ICD data as also the mortality data (2) between 2001 and 2005 was evaluated. The sentinella data for the period between 1995 and 1998 could not be projected because the data base was missing, and there are no evaluations after 2001.

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According to the Sentinella data, there were approximately 378 500 cases of influenza per annum during the period of observation (ranging from 250 000 to 500 000), which corresponds to an average incidence of approximately 4 500 per 100 000 inhabitants per annum (fig 1). These figures are similar to the data collected in neighbouring Switzerland (3) and Germany (4). Figure 1: Influenza cases 1992-2001: Projection of the Sentinella data by ARGE Influenza

2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 0 100 200 300 cases in 1000 400 500 600

On account of the switch to ICD version 10 at the turn of 2000/2001 and the differences in the documentation which occurred as a result of the switch (particularly as far as the classification of influenza with confirmed influenza viruses is concerned), a time series analysis which went back beyond the above date was waived and the evaluation was limited to the data of the years 20012005 (with uniform ICD-10 classification). According to this data an average of 2 100 influenza cases had to be hospitalised per annum nationwide in Austria between 2001 and 2005 (ranging from 1 894 to 2 327), which corresponds to a “hospitalisation” incidence of approximately 28 per 100 000 (male and female) inhabitants per annum (fig 2). In these years, around 14% (a yearly average of 295) of the patients admitted to hospital were infected with confirmed influenza viruses (an incidence of 3.7 per 100 000 inhabitants).

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Influenza Pandemic Plan Figure 2: Hospital admission rate 2001-2005 (influenza, ICD10 J10x-J11x in primary or secondary diagnosis) - admissions per 100 000 inhabitants and year*)

< 11 >= 11 and < 15 >= 15 and < 21 >= 21 and < 31 >= 31

*)

Sources: BMGFJ – documentation of diagnoses and procedures; ST.AT - population 2001-2005; calculations by GÖG/ÖBIG

standardised rate (standard population = European population)

Around 15% of the influenza patients went on to contract pneumonia (316 persons per annum, an incidence of 3.8 per 100 000). 40% of the influenza patients who went on to contract pneumonia were found to have confirmed influenza viruses according to hospital discharge data (fig 3).

46

Influenza Pandemic Plan Figure 3: Hospital admission rate 2001-2005 (influenza with pneumonia, ICD10 J100 and J110 in primary or secondary diagnosis) – admissions per 100 000 inhabitants and year*)

< 1.5 >= 1.5 and < 2.0 >= 2.0 and < 2.5 >= 2.5 and < 4.0 >= 4.0 0

*)

Sources: BMGFJ – documentation of diagnoses and procedures; ST.AT - population 2001-2005; calculations by GÖG/ÖBIG

standardised rate (standard population = European population)

According to the cause of death statistics published by “Statistik Austria”, 127 deaths were caused by influenza or complications resulting from it between 2001 and 2005, which is an incidence of 0.2 in 100 000 (fig 4). Deaths from secondary illnesses are not included, as no ICD10 codes are available. The actual death rate is therefore probably much higher.

47

Influenza Pandemic Plan Figure 4: Mortality 2001-2005 (influenza, ICD10 J10x-J11x as main cause of death) – number of deaths per 100 000 inhabitants and year*)

< 0.2 >= 0.2 and < 0.3 >= 0.3 and < 0.4 >= 0.4 and < 0.6 >= 0.6 0

*) standardised mortality (standard population = European population)

Sources: ST.AT – mortality register 2001-2005, population 2001-2005; calculations by GÖG/ÖBIG

2.2. Vaccination coverage rates
Determining the vaccination coverage rates is problematic for several reasons: • The vaccination has to be carried out afresh every year. This means that the rates have to be calculated each year recurrently • The vaccination is not part of the national “Vaccination Concept” The following methods for calculating the vaccination coverage rates are available: • The cohort model (=the proportion of vaccinated persons to the total number of a birth cohort) • Individual vaccination record (=determining the vaccination coverage rate on the base of records pertaining to individual persons) If these particulars are not available, vaccination activity can be roughly determined via vaccine consumption. In Austria, however, the vaccination coverage rate cannot be determined by these methods for the following reasons: • The obligation to collect the vaccination coverage rates only applies to those vaccinations which are financed by the Federal Republic, the provinces and the National Health Authorities and which are offered to the population free of

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Influenza Pandemic Plan

charge. As influenza is not part of the vaccination concept, there is no obligation to collect the data of vaccination coverage rates annually • As the vaccine is not purchased centrally and as, moreover, there are vaccines from several firms on the market, it is not possible to calculate vaccine consumption. One can only ask the firms how much vaccine is produced for Austria as a whole

A serious calculation of the vaccination coverage rates would only be possible at the moment if all those undertaking vaccinations were to collect and report the number of persons vaccinated per year of birth or at least the amount of vaccine used. Until then poll results will have to be used (5). Thus in 2003, a randomised study showed that the average vaccination coverage for persons over 15 was at the moment only around 17% (=a total of 1.1. million vaccinations). Particularly younger people under 40 show a lack of health awareness, as in this group the vaccination coverage is only 15%. In contrast, at least every third senior citizen over 60 has been vaccinated (=a vaccination coverage of 33%). Ignorance of the dangers of getting influenza as also trusting in one’s own physical robustness are the main reasons why risk awareness is so poor. Bibliographical references: 1. ARGE Influenza analysis for the period 1992-2001, without 1995 and 1998 (http://:www.arge-influenza.at ). Basic data: M15 – Vienna taking urban demographic structure into consideration 2. ÖBIG (= Austrian Federal Institute for Health Matters) analysis, http://www.oebig.at; Data sources: The diagnoses and performance documentation of Austrian hospitals (BMGF) or the causes of death statistics (“Statistik Austria”) 3. Anonymous. Recommendations for the Prevention of Influenza. Federal Health Office in cooperation with the influenza working group and the Swiss commission for vaccination issues. Supplement XIII, August 2000 (http://www.bag.ch ) 4. Anonymous (http://www.rki.de ) 5. Anonymous. Opinion poll Influenza in the Austrian Population Feb/March 2003. “Fessel – GfK”, Institute for market research, Vienna, 2003

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Influenza Pandemic Plan

3. Surveillance
The National Reference Centre for Influenza (NRI) is responsible for surveillance. The NRI consists of two competence centres: • • The Institute for Medical Microbiology and Hygiene Vienna (NRI Epidemiology) known as AGES The Institute for Virology at the medical school of Vienna University (NRI Laboratory)

3.1. The national reference centre for influenza – epidemiology
(NRI Epidemiology) • Surveillance of influenza occurrence by means of the Sentinella System: The system is based on the weekly reports sent in (throughout the year) by a network of doctors experienced in general, internal or pediatrical medicine of patients suspected of having influenza, which document the age, gender, complications and vaccination status of each patient and the number of deaths from influenza. Certain of these doctors send in smears for virus isolation and classification to the NRI laboratory. The results are forwarded to NRI Epidemiology every week The health insurance institutions in the provinces report the number of persons who have contracted influenza or influenza-like illnesses to ICD 10 weekly Microbiological institutes/laboratories send in weekly reports on confirmed influenza cases With a time delay of one year, the death rate statistics for influenza and pneumonia categorised into age groups provide important data for the epidemiological analysis of influenza activity in Austria The NRI exchanges information with other European countries and with the WHO o The WHO monitors influenza activity worldwide in order to be able to draw attention to the threat of a pandemic in good time. Information on antigenic mutations in influenza viruses are sent to the national reference centres. Similarly, the WHO prescribes the composition of the current vaccine Austria keeps abreast of the epidemiological situation in Europe by exchanging information with other European countries EISS1 and EUROGROG2

• •

o

1EISS (=European Influenza Surveillance Scheme) 2EUROGROG (=Groupe d’observation de la grippe)

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Influenza Pandemic Plan

3.2. National reference centre of influenza – laboratory
(NRI Llaboratory) Influenza viruses from samples which doctors have taken from patients with influenza and sent in, are isolated and classified at the Virological Institute of Vienna University Medical School. The NRI laboratory sends this data in weekly to NRI Epidemiology with details of the available data of the patients such as age, gender, clinical complications and virus type, as also the method for detection.

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Influenza Pandemic Plan

4. Drugs
4.1. General information on effective influenza virostatics
From the epidemiological point of view, it is necessary to protect those in the population who are particularly susceptible or prone to infection from contracting influenza as early as possible. In order to bridge the time gap between the public announcement of a pandemic, the identification and availability of the virus, the manufacture of a suitable vaccine, the vaccination of the population and until individuals have built up sufficient immunity, and also in order to be able to take prophylactic and therapeutic measures in good time during the time gap (which will foreseeable be about twelve weeks), extensive use of suitable virostatics should be considered. In principle, two groups of drugs are available: Amantadine and neuraminidase inhibitors.

4.1.1. Amantadine
Amantadine (and Rimantadine - not licensed in Austria), which has been used for influenza prophylaxis and therapy for more than 30 years, is an ion channel blocker of the M2 ion channel in the membrane of influenza A viruses. It prevents the uncoating (blocking the release of the virus genome) of viral nucleic acid in the infected cell. This medication does not seem suitable for extensive use in a pandemic for the following reasons: • The possibility that after a short treatment time (2-3 days) resistant variants of the virus will appear which could spread and would therefore soon render this therapy useless Amantadine has a narrower spectrum of activity than the newer drugs which have proved specifically effective for influenza A and B. It is, moreover, only usable for influenza A. This seems adequate, as on account of the antigen shift, a pandemic can only be caused by the influenza A virus, according to expert opinion. The disadvantage is, however, that Amantadine is not effective for possible influenza B infections which may break out at the same time as a pandemic First analyses of the Avian-Influenza-Virus Infection (H5N1) in poultry by the WHO Global Influenza Laboratory Network, cases of which have repeatedly occurred of late, especially in chickens (so-called chicken flu) have shown that these particular viruses seem to be resistant to Amantadine. As it is precisely also these viruses which come into question as a possible reservoir for forming a human pathological variant which could cause a pandemic, one can assume that in that case Amantadine would be completely useless

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Influenza Pandemic Plan

The side effect profile and contraindications of Amantadine, moreover, make it appear in a far less favourable light than the other available drugs for treating Influenza A infections

4.1.2. Neuraminidase inhibitors
Neuraminidase inhibitors represent the group of newer and specifically effective drugs against influenza A and B today. The active substances available are Zanamivir and Oseltamivir. Both substances block the neuraminidase of the influenza virus and in this way stop the release of newly formed virus particles from already infected cells. Both Zanamivir and Oseltamivir are effective against all nine known neuraminidase (N) subtypes of the influenza A virus as also against the neuraminidase of the influenza B virus. It can therefore be assumed that, according to what is known today, it would also be effective against those human pathogenic virus variants that lead to a pandemic which can be caused by the agent of so-called chicken flu, - the avian-influenza-virus (H5N1). In the case of both substances, one has 36-48 hours after the appearance of first symptoms in which to begin the therapy and achieve successful treatment. New investigations show that in principle therapy should begin as early as possible, optimally within the first 12 hours. Oseltamivir and more recently also Zanamivir have been licensed for the therapy and prophylaxis of influenza infections in Austria. The way the drugs are administered, however, (Oseltamivir is administered per os while Zanamivir is administered by inhaler) means that Oseltamivir is preferable for use in an influenza pandemic. A drug that has to be inhaled like Zanamivir does not seem very practical for use in a pandemic. (For this reason Zanamivir is also unsuitable for small children/children and unlike Oseltamivir licensed for children older than 5 years.) Furthermore, Zanamivir can lead to an acute bronchospasm with a serious reduction of respiratory function in patients with serious asthma or respiratory disease as also in older patients. As far as the problem of possible resistance development is concerned, laboratory tests have shown that resistance to both neuraminidase inhibitors develop less frequently than to Amantadine, although the latest tests for Oseltamivir (Kiso et al., Lancet, 2004; Le et al., Nature, 2005; De Jong et al., NEJM, 2005) also show a somewhat higher than expected appearance of resistant mutants in neuraminidase inhibitors. The final significance of these results in view of the problem of clinically relevant resistance development when this group of substances is widely used as in the case of a pandemic, cannot be exactly estimated at the present time, however. From today’s point of view, the fact that the appearance of resistant virus variants in neuraminidase inhibitors has proved lower in clinical tests gives hope that the agent will remain sensitive to these substances for a sufficiently long time. The systemic compatibility of both neuraminidase inhibitors can generally be classified as acceptable to good. The possible side effects of treatment with Oseltamivir are of a gastrointestinal nature (nausea, vomiting) and were usually comparable with the results of the side effects observed in a placebo group or only somewhat higher (5% more vomiting than in the placebo group). As far as
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Influenza Pandemic Plan

Zanamivir is concerned, moreover, only a very slight systemic exposition is to be reckoned with because it is administered by inhaler. The side effects are therefore concentrated above all on the place of administration. Reports of bronchospasm or dyspnea were very rare. It is possible to deduct a very good safety/effectiveness ratio not only in comparison with Amantadine from the above data. The expected side effects of Oseltamivir or Zanamivir when used extensively can therefore be said to be acceptable. In case of a pandemic, above all Oseltamivir, primarily because it is suitable for children from the age of one upwards not only for therapy but also for preventive purposes, that is for prophylaxis (seasonally as well as postexpositionally), and because it is practical to administer as it is available in tablet as well as suspension form, is at the moment the most suitable virostatic substance on the market for use in a pandemic. The advantages of Oseltamivir: • Therapy and • Prophylaxis: seasonal and postexpositional • Suitable for children from one year upwards as therapy and prophylaxis • Few side effects/ safe administration • Practical to take

4.2 Prophylaxis/therapy with Oseltamivir/Tamiflu® (Roche)
The reason for the Oseltamivir therapy or prophylaxis is, as stated above, primarily to bridge the time gap until a sufficient supply of an effective vaccine is available plus the time it takes for a protective immunity to develop. Extensive use of Oseltamivir in a pandemic would therefore seem to be necessary in order to keep the mortality and morbidity rate in the population as low as possible.

4.2.1. Prophylaxis with Tamiflu®:
An adequate and early prophylaxis with Oseltamivir which is administered in good time is above all necessary for those persons who are particularly exposed or endangered persons. Extensive prophylaxis for those responsible for keeping up the infrastructure should also be aimed at, as also hospital and nursing personnel. The latter are necessary not only for looking after those who are already infected and are therefore themselves exposed to a greater risk, but they in their turn are also a source of infection which should not be underestimated. (Potter et al., J Infect Dis, 1997). In principle, one must distinguish between two different forms of prophylaxis: • Post exposition prophylaxis: for persons who have been in contact with infected patients and who have not been vaccinated if chemoprophylaxis can be begun within 48 hours

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Influenza Pandemic Plan

Seasonal prophylaxis: for persons who have not been vaccinated, regardless of whether they have been in contact with infected patients, for the duration of the influenza wave until immunisation protection is assured

During a pandemic above all seasonal prophylaxis should therefore be used. It is helpful that there is no interaction between prophylaxis with Oseltamivir and the development of immunisation protection and if possible to bridge the time gap between protective vaccination and immunization protection. It must be stated, however, that a high compliance (that is regular and reliable administration of the drug) is decisive for a successful prophylaxis and that this must also be appropriately communicated to the population. Oseltamivir is licensed for prophylaxis for adults and children from one year upwards. The dosage is: • Adults and young people over 13: 75mg Oseltamivir once a day for 10 days for postexpositional prophylaxis or up to 6 weeks for seasonal prophylaxis. Dosage adjustment for creatinine clearance 10-30 mL/min to 1x 75mg every second day or 30mg suspension once daily (see also technical information) Children over one year: (only use suspension) dependent on their weight: < > > > 15kg: 15-23kg: 23-40kg: 40kg: 30mg 45mg 60mg 75mg once once once once a a a a day day day day

4.2.2. Therapy
For those persons who have already been infected, Oseltamivir can have a causal-therapeutic effect. The drug must, however, be administered as soon as possible, optimally within the first twelve hours (at the latest within 48 hours) after the appearance of the first symptoms. The latest research again confirms the necessity of beginning treatment as early as possible. The effect of the treatment consists in relieving the symptoms (e.g. fever, headaches, myalgia, coughing) as also in shortening the duration of the illness. Typical complications (e.g. bacterial infections of the lower respiratory tracts, mainly bronchitis) are moreover diminished. The reduced virus secretion which has been observed in treated patients could moreover have a positive effect on the infection rate. Beginning treatment as early as possible which, as seen above, is particularly important if it is to be effective, also raises the question of appropriate diagnosis: The meaningfulness of a purely cinical diagnosis is dependent on the influenza incidence rate. While the predictive value of the typical influenza symptoms is relatively unimportant for a clinical diagnosis at times when the incidence of
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Influenza Pandemic Plan

influenza is relatively low, in a pandemic, however, it is possible to diagnose influenza with adequate accuracy on the basis of the symptoms. It is estimated that more than 70% of genuine influenza cases can be accurately diagnosed through clinical diagnosis. This means that extensive laboratory tests are not necessary. Using various quick tests is at the moment still disputed. Sensitivity and specificity have not yet been sufficiently evaluated and the cost plays an essential role in extensive use. Furthermore, the diagnosis rate in recognising cases of influenza is not a great deal higher than 70%. For these reasons, during a pandemic, a clinical diagnosis should already be made at the first consultation followed immediately by prompt treatment which is essential if the treatment is to be effective. Oseltamivir is licensed for the therapy of adults and children from one year upwards. The dosage is as follows: • Adults and young people of 13 and more: 75mg Oseltamivir twice a day for 5 days adjustment of dosage for creatinine clearance 10-30 mL/min to 75mg once a day or 30mg suspension twice a day (see also summary of product characteristics) Children from age one upwards: (use only suspension) dependent on weight: <15kg: 30 mg twice daily >15-23kg: 45 mg twice daily >23-40kg: 60 mg twice daily >40kg: 75 mg twice daily for 5 days in each case

The latest studies indicate that (regardless of the specific resistance position of the agent), a higher dosage or taking Oseltamivir for a longer time period than shown above might be necessary in a pandemic. The dosage recommendations for an emergency will therefore need to be adjusted to the actual situation shortly beforehand.

4.2.3. Dosage form
Tamiflu® is available in two bio-equivalent dosage forms – as a hard capsule and a powder for preparation of a suspension. So that it can also be administered to children, stocking supplies should concentrate on the suspension form although the shelf-life of the suspension is shorter than that of the capsule, namely only 2 years, while the capsule has a shelf-life of 5 years. As it is planned to use the drug extensively in the case of a pandemic, special dosage forms and package sizes will also be needed. For this purpose, the manufacturer is offering the active substance in barrels of 107 litres in volume containing 7kg of Oseltamivirphosphate (equivalent to 5.33 kg pure active substance). As things stand at the moment, these will only be supplied in the case of a pandemic to be made up as a formula magistralis. They combine the advantage of being suitable for children with the advantage of an increased
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Influenza Pandemic Plan

shelf-life (at the moment the shelf-life for this form of storage has been confirmed as 5 years and may possibly be extended to 10 years). Furthermore, the barrels are more advantageous as far as storage and costs are concerned. The cost of the necessary active substance for the treatment of a patient is approximately half that of the treatment with hard capsules. The preparation of the solution which is ready for use will be undertaken by special pharmaceutical personnel at special locations or facilities (presumably pharmacies and hospital pharmacies) who will be determined according to demand. For the preparation of one barrel the following are needed: • • • 355.3 litres of aqueous 0,1% sodium benzoate solution = 355.3 litres H²O and 355.3g of sodium benzoate, as also for distribution among the population 7106 dark 50ml bottles for bottling as also for attaching a dispenser/syringe 7106 oral dispensers (with a 5ml marking) or 5ml syringes will be needed

The dosage for the solution prepared from the barrels will be measured in ml: • • 1ml of the prepared and ready for use solution contains 15mg of Oseltamivir 5ml (= individual dose for adults) therefore contains 75mg of Oseltamivir

The active substance content of one barrel is theoretically enough for the individual treatment of 7 106 infected persons or for post-expositional prophylactic treatment of the same number of healthy persons or, alternatively, assuming that treatment is licensed for a total period of 6 weeks, enough for 1 692 seasonal prophylaxes.

4.3. Prophylaxis/therapy with Zanamivir/Relenza® (GSK)
As an alternative to a prophylaxis/therapy with the substance Oseltamivir, treatment with Zanamivir can be considered. It is the second substance from the group of neuraminidase inhibitors which has been licensed in Austria. Even if Relenza® does not seem equally suitable for all members of the population because of the way it is administered (a powder to be inhaled), to date it is possibly a valuable contribution to the preparations for a pandemic. On the one hand, possible bottlenecks in supplies of Oseltamivir can be compensated or bridged with Zanamivir. On the other hand, should resistance to the pandemic virus develop, it could be advantageous to have a second effective substance available as an alternative. Both substances block the function of viral neuraminidase protein and therefore have identical targets, so there is certainly the possibility of cross-resistance. A more recent investigation, however, showed that even when the virus already showed increased resistance to the one substance, it was still adequately sensitive to the other (Le et al., Nature, 2005). Relenza® is licensed for the prophylaxis and therapy of adults and children of over 5 years of age. In a pandemic, Tamiflu® suspension must therefore be used for children under 5 years (licensed for children over one – see above).

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4.3.1. Prophylaxis with Relenza® :
Relenza® can be used both for post-expositional and seasonal prophylaxis. As with Tamiflu®, timely administration is decisive for post-expositional prophylaxis after contact with a person clinically diagnosed as having influenza. The drug should therefore be administered as soon as possible, at latest 36 hours after contact. • Adults and children over 5 years Two inhalations once a day (that is 2x5mg of Zanamivir once a day) for 10 days as a post-expositional prophylaxis or up to 28 days when used as a seasonal prophylaxis. Dosage adjustment in cases of kidney or liver insufficiency, or in the case of older persons is not necessary

4.3.2. Therapy with Relenza®:
Relenza®, too, like Tamiflu® must be taken as soon as possible in order to have a therapeutic effect. Optimally, it should therefore be taken within the first 12 hours after the first symptoms appear (but within 36 hours at the latest by children and 48 hours by adults). As with Tamiflu®, treatment relieves the symptoms (e.g. fever, headache, myalgia and coughing) and also shortens the duration of the illness. In a pooled analysis, it was also possible to show that the typical complications of influenza are curtailed. • Adults and children over 5 years Two inhalations twice a day (=5mg of Zanamivir twice as day) for 5 days, i.e. the dosage for one day is 20mg. It is not necessary to adjust the dosage for kidney or liver insufficiency, or for older persons (see also summary of product characteristics)

4.3.3. Dosage forms
Relenza® is available in folding boxes which each contain 5 round aluminium foil disks (called rotadisk with a shelf life of 5 years. The substance is packed in 4 evenly piled blisters on each of these rotadisks (the contents of 2 blisters equal one dosage, each blister contains 5mg of Zanamivir). In this way, the substance is available as a powder for inhalation. A plastic inhaler based on inspiration (called a diskhaler) is enclosed for measuring out single doses from the rotadisk. A rotadisk is placed in the plastic inhaler. When the diskhaler is activated (=raising the lid as far as it goes) a rotadisk blister is pierced and the substance can now be administered. With the following deep inhalation the powder gets through the mouth piece in the respiratory tract (for exact instructions on how to use the inhaler see directions). It is also planned to make Relenza® available in bulk for better stockpiling. It will foreseeable be in boxes each of which will contain 77 inhalers with 5 rotadisks

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Influenza Pandemic Plan

and 77 directions for use plus instructions for the correct distribution of the bulk ware components. The complete content of the box would theoretically last for a single use of 77 ill persons or for the same number of postexpositional prophylaxic in healthy people, or, alternatively, starting from a licensed complete duration of treatment of 4 weeks for 27 seasonal prophylaxes.

4.4. Accompanying therapy – antibiotics/NSAR
The accompanying treatment for influenza infections that have already broken out depends on the seriousness of the illness and the patient’s general condition. In most cases symptomatic treatment will suffice (besides using certain virostatics as described above): relieving pain and reducing fever with the appropriate drugs, using expectorants or antitussives (but not in combination!) and above all sufficient rest and care. Care must be taken when reducing fever in children: Acetylsalicylic acid must never be used to reduce fever in children with influenza as it can cause the socalled Reye Syndrom: this is a serious form of encephalopathy with fatty degeneration of the liver cells and symptoms such as vomiting, fever, dizziness and coma with a fatality rate of approximately 25%. Up to puberty, therefore, ASS is contraindicated for virus infections in children. Complications which require treatment over and above symptomatic therapy usually occur more often in patients with chronic heart, circulatory or lung diseases and in older patients. In the majority of cases the complications are caused by secondary bacterial superinfections with Haemophilus influenzae or Streptococcus pneumoniae (Pneumococci), which are often accompanied by pneumonia. Bacterial sinus infections (sinusitis) and bacterial ear infections (otitis media) can also occur. In such cases treatment with the appropriate antibiotics is indicated. Depending on the virulence of the agent or the seriousness of the illness (primary viral or secondary superinfected pneumonia with respiratory insufficiency or systemic vasculitides with multiple organ failure etc…) can, however, necessitate acute intensive medical care.

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5. Vaccines
Producing and making an effective vaccine that is well tolerable available as soon as possible is the most urgent target in the case of an impending pandemic. Already in the inter-pandemic phase, this task requires the most extensive preparation possible as far as production, testing and licensing procedures for the vaccine are concerned on the part of the manufacturers and licensing authorities.

5.1. Manufacture, documentation and licensing of a safe and effective vaccine
The Vaccine Working Party (VWP) of the EMEA (European Medicines Agency) has for this reason produced several guidelines (adopted March 2004 and June 2005). On the one hand, the guidelines are to guarantee the quality, safety and effectiveness of the vaccine, and on the other hand, to ensure that the licensing authorities work together with the manufacturers and the WHO. In 2005, the EMEA published a draft crisis management plan in the case of an influenza pandemic for public consultation. The plan aims to establish efficient procedures for evaluating and authorising pandemic influenza vaccines in a centralised procedure and for the surveillance of vaccines and antiviral drugs for a potential pandemic. The guidelines are summarised below: • “Guideline on Dossier Structure and Content for Pandemic Influenza Vaccine Marketing Authorisation Application” (EMEA/CPMP/VEG/4717/03) • http://www.emea.europa.eu/pdfs/human/vwp/471703en.pdf • “Guideline on Submission of Marketing Authorisation Applications for Pandemic Influenza Vaccines through Centralised Procedure” (EMEA/CPMP/VEG/4986/03) • http://www.emea.europa.eu/pdfs/human/vwp/498603en.pdf • “Core SPC for Pandemic Influenza Vaccines” (EMEA/CPMP/VEG/193031/2004) http://www.emea.europa.eu/pdfs/human/vwp/19303104en.pdf The following documents are still being worked on: • “EMEA Pandemic Influenza crisis management plan for the evaluation and maintenance of Pandemic Influenza vaccines and antivirals” (EMEA/397403/2005; Released for consultation November 2005) http://www.emea.europa.eu/pdfs/human/vwp/39740305en.pdf • “Guideline on dossier structure and content of Marketing Authorisation applications for Influenza vaccines with avian strains with a pandemic potential for use outside of the core dossier context (EMEA/CHMP/VWP/263499/2006; Released for consultation July 2006) http://www.emea.europa.eu/pdfs/human/vwp/26349906en.pdf

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5.1.1. Quality
It is not possible from today’s point of view to give details about the final formula of an influenza pandemic vaccine. The production and final formulation of an influenza pandemic vaccine will differ in certain aspects from the influence vaccine used in the inter-pandemic phase. It is very probable that such a vaccine will be an inactive, monovalent and adjuvant “whole-virus” vaccine with preservatives, whereby different manufacturers have different approaches. As a far greater amount of the vaccine will be needed in a pandemic and on account of the fact that it will have to be available as quickly as possible, it is probable that no further processing of the cell surface antigens will follow after inactivation. The advantages of such a “whole-virus” vaccine are less loss of large amounts of the antigen needed and a better immunogenicity. In order further to provide for sufficient immunogenicity and to keep the needed amount of antigen for a single dose low, it can be assumed that the vaccine will be adjuvanted. Should an influenza pandemic vaccine be packed in multiple dosage containers for reasons of faster production, better stability (cooling) and simpler, roomsaving storage, from today’s point of view, it will not be possible to avoid adding the preservative Thiomersal. At the moment, however, the tendency is to fill disposable syringes. During the production of the vaccine strain, it can be assumed that gene technology (reverse genetics) will be used. 5.1.1.1. Production Propagation of the vaccine virus can – as in the influenza vaccines which are on the market at the moment – take place in embryonated hens`eggs or by using the cell culture method. “Vero” or “MDCK” cells, which have been used for cell cultures for many years, are used for this purpose. They are biologically and genetically very well characterised and free of pathogens and have been used for the production of other vaccines. It is very probable that the large amounts of vaccine virus required in a pandemic can be produced more quickly with the cell culture method. Furthermore, experts assume that greater purity can be achieved with the cell culture method than with embryonated hens’ eggs. Besides the general EMEA guidelines and monographs of the Pharmacopoeia and the monograph of the European Medicines “Manual for Virus Promulgation in embryonated hens’eggs”, the “Note for Guidance on Cell Culture inactivated Influenza Vaccines” (CPMP/BWP/2490/00) should be taken into account in production.

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5.1.1.1.1. The reference virus The typing of the Influenza A viruses occurs on the basis of the virus’s surface proteins hemagglutinin (H) and neuraminidase (N). Ducks were identified as the original hosts of the last three great pandemics caused by influenza A viruses ( “Spanish Flu”, H1N1, 1918-20; “Asian Flu”, H2N2, 1957-60; “Hong-Kong Flu” H3N2, 1968-70). New influenza A viruses can evolve at any time in “avian influenza viruses” through “antigenic drift” (high rate of point mutations) and/or through “antigenic shift” (reassortment of the eight-part virus genome) which can in the final instance become contagious and pathogenic for human beings. Mixed infections in pigs have primarily been made responsible for the reassorting of viral genomes. As 16 different H-subtypes and 9 N-subtypes are known at the moment, there are many theoretical combination possibilities. The possibility of antigenic drift in influenza viruses mentioned above manifoldly multiplies the number of possible variants. For this reason it is not possible to characterise a pandemic virus genetically and antigenetically and to produce a preventive vaccine before the potential pandemic virus actually evolves. Most experts assume that future influenza A viruses with the potential for a pandemic will probably also be derived from avian influenza viruses. WHO, EMEA, international research institutes and health authorities therefore attach particular importance to those subtypes in the “three great epidemics” which already proved to have pandemic potential (=H1 to H3; see above). No less attention is being paid to subtype H5N1 which has been circulating in wild and domestic fowl in Asia since at least 2003, and for which there is as yet no guaranteed proof of human-human transmission, but which is also highly pathogenetic for humans. High priority is also being given to subtypes H7 and H9, which are contagious for humans but for which again there is as yet no guaranteed proof of humanhuman transmission. The actual virus strain for vaccine production will be determined by the WHO or by a reference laboratory designated for this purpose by the WHO and then made available. 5.1.1.1.2. Possible use of gene technology As there is no absolute guarantee that a pandemic virus will be propagatable quickly and in large quantities, it is probable that gene technology will be used to solve this problem. The possibility of very high pathogenicity could, moreover, make it impossible for the manufacturer, for safety reasons, to produce a vaccine directly from this virus. Both these potential problems for vaccine production (bad propagatability and high pathogenicity) could be solved by the gene-technological method known as “reverse genetics”. With this method, “virus hybrids” which carry the surface proteins H and N of the pandemic virus mainly responsible for immunogenicity are produced in a class 3 biosafety laboratory. The other genes derive from a not very pathogenetic but at the same time well propagatable influenza A virus.

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Influenza Pandemic Plan

The production of such a vaccine strain was succesfully tested at the NIBSC (National Institute for Biological Standards and Controls, UK) and should be carried out in the case of a pandemic. Subsequently, this gene-technologically produced not very pathogenic and well propagatable virus strain could then be made available to the vaccine manufacturers. Such a procedure would be in the charge of the WHO.

5.1.2. Pre-clinical testing
An adjuvantisation above all of the purity of the vaccine, the type of antigen (“whole-virus or “purified antigen”) and the amount of antigen are responsible for the reactogenicity. In this case, the knowledge and experience of more than 50 years of “influenza vaccine” research will be included in a benefit-risk analysis so that a shorter period of pre-clinical testing may possibly be considered adequate.

5.1.3. Clinical testing
Clinical testing should verify adequate immunogenicity and the safety of the vaccine. The evaluation of a suitable vaccine scheme is of particular significance in order to be able to guarantee the efficacy. The status of the population, the characteristics of the vaccine (adjuvantisation, antigen amount, type of antigen) and the possible infection pressure must all be taken into consideration in the case of a pandemic. A booster vaccination will probably be necessary for a completely unprotected population when exposed to a pandemic. Clinical development must take this into account in correspondence with the above cited EMEA guidelines.

5.1.4. Summary of product characteristics and package leaflet instructions for use
The professional and general instructions should be consulted for exact details for the safe and effective use in the case of a pandemic. See also:”Core SPC for Pandemic Influenza Vaccines” EMEA/CPMP/VEG/193031/2004 http://www.emea.europa.eu/pdfs/human/vwp/19303104en.pdf

5.2. Marketing authorisation procedure
See: “Guideline on the Submission of Marketing Authorisation Applications for Pandemic Influenza Vaccines through the Centralised Procedure”. (EMEA/CPMP/VEG/4986/03) http://www.emea.eu.int/pdfs/human/veg/498603en.pdf

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Influenza Pandemic Plan

Licensing procedure serves the purpose of checking the quality, safety and efficacy of the vaccine. At the same time, in a pandemic, any unnecessary loss of time must be avoided. For this reason joint coordinated action on the part of the licensing authorities and vaccine manufacturers is imperative already in the inter-pandemic period. The procedure for marketing authorisation of a pandemic influenza vaccine will take place within the framework of a “centralised licensing procedure” of which the EMEA will be in charge. In case it is needed, a 2-step opening procedure is characteristic for the marketing authorisation procedure of a pandemic vaccine (mock up authorisation and pandemic variation). That means that already BEFORE the appearance of a pandemic (that is already in the inter-pandemic phase), a so-called “CorePandemic” dossier is handed in and examined. As the pandemic virus is not yet available, a “model virus” is used instead. The EMEA guidelines (EMEA/CPMP/VEG/4717/03) give recommendations and examples for selecting such a “model virus” which should be used for a so-called “Mock-up” vaccine (“Model vaccine”). The second stage of the licensing procedure and the authorisation to put the vaccine on the market does not take place until the actual pandemic occurs after the WHO has made the necessary reference virus available for the manufacture of the actual pandemic vaccine. This second authorisation stage is called a “pandemic variation” (modification procedure). In this variation the model virus is replaced by the actual pandemic virus. In order to avoid any unnecessary loss of time, the “Joint EMEA-Industry Task Force” has been set up which is to guarantee the coordinated procedure already during the interpandemic phase and also in the case of a pandemic. The above cited EMEA guidelines concerning authorisation lay down the course of the centralised authorisation procedure in detail in chronological and organisational liaison with the WHO alarm system in an influenza pandemic. The marketing authorisation within the framework of a centralised authorisation procedure applies to all the member states of the EEA (European Economic Area).

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SUPPLEMENT
Appendix 1 -11

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Influenza Pandemic Plan

APPENDIX 1:

EXPLANATORY LEAFLET – INFLUENZA – PANDEMIC
What is influenza? Influenza is a highly infectious disease of the respiratory tracts which is caused by the influenza virus. What are the symptoms? (in the pandemic: in accordance with the WHO – case definition) • • • • • • Fever over 38°C Muscle pain Dry cough Headache Sore throat Fatique

How is influenza spread? Influenza is spread through so-called droplets which are exhaled from the mouth or nose by coughing or sneezing. Transmission is also possible by contact with surfaces contaminated with the influenza virus (e.g. work surfaces, objects) or via hands. Adults are usually infectious for five days after the appearance of the first symptoms, children for seven days or longer. How long does the illness last? Approximately one week if there are no complications. How can infection with and the spread of influenza be prevented? • • • • • • • • Avoid crowds (cinemas, theatres, markets, means of mass transportation) (Restrictions will be announced when required: e.g. only go to work, school or university if absolutely necessary; do not send your child to the kindergarten) Avoid close contact with other people Only do absolutely necessary shopping Only use own dishes, glasses and cutlery Avoid hand contact (shaking hands) (Wear protective mouth masks) (Have yourself and your children vaccinated with the current vaccine which may give partial protection)

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Influenza Pandemic Plan

If you do get influenza Avoid close contact with relatives and friends who have not been infected Only use disposable paper handkerchiefs and dispose them safely in plastic bags • Drink a lot of fluids • Avoid physical activities • You must stay in bed • Take your prescribed medicine regularly • Avoid aspirin if you are under 15 or if you take certain coagulation inhibitors • If in severe pain use a standard painkiller like paracetamol (dosage prescribed by a doctor or as described in package leaflet instructions for use, a maximum of 8x500 mg per day) Contact your general practitioner if you notice that you have influenza symptoms and if, moreover, one of the following conditions apply to you: • • • You are over 60 Pregnancy A certain medication therapy because of: o asthma (oral steroids, hospitalisation) o emphysema or chronic obstructive respiratory disease o diabetes o heart disease o organ transplants o weak immune system (e.g. steroids or chemotherapy) • •

Contact your doctor immediately if you have influenza and, despite the fact that you have kept to the above recommendations, you notice or experience one of the following: • • • • • A rash Extreme fatigue (drowsiness) Your condition deteriorates you are short of breath Piercing chest pain when you breathe in deeply

Specific therapy and vaccination Will be defined when the situation requires it Do antibiotics help? Antibiotics have no effect on viruses and are thus not effective against influenza. Nevertheless, doctors sometimes prescribe antibiotics for virus infections in order to prevent bacterial infection of the mucous membranes (tissues). Further information can be obtained via the Info-Hotline, the homepage of the Ministry of Health, the provincial health authorities,..

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Risk stratification for CAP (= Community Acquired Pneumonia)* *Taken from CliniCum, special edition 10/2003: Expert statement on CAP patronage: ÖGCH (= Austrian Society for Chemotherapy) and ÖGLUT (= Austrian Society for Lung Diseases and Tuberculosis)

Pneumonia contracted by out-patients
CAP –Stratification

Thorax X-Ray INFILTRATION

Influenza Pandemic Plan

APPENDIX 2:

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Group I

Group II

Group III

Clinically STABLE ONE comorbidity Age < 65

Clinically ± STABLE

Clinically UNSTABLE more than ONE comorbidity independent of age

Clinically UNSTABLE ONE morbidity Age > 65

NO comorbidity NO age restriction

Out-patient Therapy I recommended

out-patient/Hospital patient Therapy II recommended

hospital patients Therapy III recommended

Antibiotic Therapy for CAP (= Community Acquired Pneumonia) according to risk groups*

*taken from CliniCum, special edition 10/2003: specialists’ statement on CAP Patronage: ÖGCH (Austrian Society for Chemotherapy) and ÖGLUT (= Austrian Society for Lung Diseases and Tuberculosis)

Children
Amoxicillin/Clac Ampicillin/Sulb Bacampicillin Cefotaxime Cefepime Cefpirome Ceftriaxone Cefodizim Ertapenem PLUS Levofloxacin Moxifloxacin 1x0,5g p.o. 1x0,4g p.o. Acitromycin Clarithromycin 3x2,2g i.v. 3x3g i.v. 3x2g i.v. 3x1,5g i.v. 3x2g i.v. 1x2g 1x1g i.v. i.v. Levofloxacin Moxifloxacin 3x1g p.o. 3x0,75g p.o. 3x0,8g p.o. Piperacillin/Taz

Group I

Group II

Group III
3x4,5g i.v.

Babies and children up to 3 months Amoxicillin 3x1g 2x2g 3x1g 2x1g 1x0,4g 2x0,4g 2x1g Azithromycin Clarithromycin Roxithromycin Telithromycin 1x0,5g 2x0,5g 2x0,3g 1x0,8g p.o. p.o. p.o. p.o. p.o. p.o. p.o. p.o. p.o. p.o. p.o.

Amoxicillin Cefadroxil Cefalexin Cefetamet-P. Cefixime Cefpodoxime Cefuroxime-A.

3x2g

i.v.

Children from 3 months to 14 years Amoxicillin Cefadroxil 50-100 mg/kg 3 ED p.o. Cefalexin Cefetamet-P. 20mg/kg 2 ED p.o. Cefixime 8 mg/kg 1 ED p.o. Cefpodoxime 5-12 mg/kg 2 ED p.o. Cefuroxime-A 20-30 mg/kg 2 ED p.o. 1x0,5g (1-)2x0,5g (1-)2x0,3g 1x0,8g p.o. p.o. p.o. p.o.

APPENDIX 3:

1x2g 1x1g

i.v. i.v.

Influenza Pandemic Plan

69
1x0,2g p.o. Amoxicillin/Clac Ampicillin/Sulb Cefamandole Cefotiam Cefuroxime Cefotaxime Ceftriaxone Cefodizim Ertapenem Levofloxacin Moxifloxacin 1x0,5g i.v. 1x0,4g i.v.

Acitromycin Clarithromycin Roxithromycin Telithromycin

1x0,5g 2x0,5g 1x0,5-1g 1x0,4g

i.v. i.v. i.v. i.v.

Acitromycin 10 mg/kg Clarithromycin 15 mg/kg Roxithromycin 5mg/kg Telithromycin from the age of

1 ED p.o. 2 ED p.o. 1 ED p.o. 12 1 ED p.o.

Doxycycline

Influenza Pandemic Plan

APPENDIX 4:

SAMPLE SHEET FOR HYGIENE FILE
Flu (Influenza)
General Agent Sample where agent prevalent Usual manner of infection Possible ways of transmission in hospitals Inform the authorities Duration of subsequent measures Accommodation Protective measures Protective smock Gloves Mouth/nose protection Protective goggles Protective cap Changing shoes Disinfecting hands Disinfecting surfaces Orthomyxoviridae Respiratory secretion Droplet infection, direct or indirect smear infection Human to human transmission with droplets, transmission through hands and objects possible No 3-5 days after the outbreak of the illness for adults and up to 7 days for children If hospitalisation is necessary: single rooms or cohort isolation Necessary Necessary (FFP3 mask with ventile) Necessary Not necessary Not necessary After taking off gloves and mask Cleaning staff: clean isolation rooms last, disinfect floors and surfaces daily Nursing personnel: disinfect medical apparatus at least once a day appropriate protective clothing must be worn. Mops and cloths must be treated in the same way as laundry It is usually necessary to disinfect the instruments within the unit in which they were used; after use, soak them in disinfectant used for instruments; follow instructions for virus efficacy, concentration and soaking time Further treatment as usual Disposable dishes should preferably be used Pack used bedlinen and patients’ clothing into plastic bags and take to laundry Wipe with surface disinfectant Disinfection within the unit Waste, particularly paper handkerchiefs, must be put into thick plastic bags and disposed of

Continuous Disinfection

Instruments

Crockery/dishes Bedlinen and patients’ clothing Patients’ rooms Cleaning hospital beds Waste

Final disinfection

Waste disposal

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Influenza Pandemic Plan

APPENDIX 5:
Influenza-reference centre for Influenza: AGES Vienna, Dr Peter Lachner: Fax 050555 37109 E-mail: peter.lachner@ages.at

Head Office of provincial health authority: __________________________

INFLUENZA – SENTINELLA FAX-REGISTRATION FORM
Year of birth Gender (m=1, f=2) Pneumonia (yes=x) Inpatient (yes=x) Vaccinated (yes=1, no 2) Death (yes=x)

Patient Nr.

Antiviral therapy Amantadine =1 Neuraminidase inhibitors =2

DOCTOR’S CODE

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APPENDIX 6:

EU – influenza case definition
(according to the decision of the commission of 19.3.02 (C(2002) 1043), which, according to decision 2119/98/EC of the European Parliament and Council, lays down the case definitions of contagious diseases that have to be reported) Clinical Description Sudden onset of illness, coughing, fever >38° C, muscle pain and/or headache Laboratory criteria • • • Confirmation of antigen or influenza virus specific RNA Agent isolation Confirmation of antibodies

Case Definition Confirmed case: Probable case: Possible case: Comment: In the case of a pandemic, the WHO will publish a case definition adjusted to the actual clinical image which the EU – Austria included – will adopt. National and international announcements will therefore be effected according to a uniform worldwide case definition – analogous to SARS. clinical case with laboratory confirmation clinical case with epidemiological connection

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Contributors
Authors (in alphabetical order)
Dr Christoph Baumgärtel, Pharmed Austria Mag Petra Falb, Pharmed Austria DI Dr Gerhard Fülöp, Gesundheit Österreich GmbH, Geschäftsbereich ÖBIG Dr Sylvia Füszl, Federal Ministry of Health, Family and Youth Dr Wolfgang Gelbmann, EFSA (=European Food Safety Authority) Univ-Prof Dr Franz. X. Heinz, Virological Institute of Vienna University Medical School DI Anton Hlava, Gesundheit Österreich GmbH, Geschäftsbereich ÖBIG Dr Ursula Karnthaler, Provincial Health Authority, Vienna Univ-Prof Dr Michael Kunze, Centre for Public Health, Medical University of Vienna Dr Peter Lachner, AGES (=Austrian Agency for Health and Food Safety) Uni-Prof Dr Theresia Popow-Kraupp, Virological Institute of Vienna University Medical School DDr Reinhild Strauss, Federal Ministry of Health, Family and Youth Univ–Prof Dr Günther Wewalka, AGES (=Austrian Agency for Health and Food Safety)

Partners from the provincial health authorities
(Federal and Provincial Working Group) (in alphabethical order)
LSD Dr Elmar Bechter (Vorarlberg), StPhys Dr Christine Bruns (Vienna), OSR Dr Alfred Gränz (Styria), LSD Dr Werner Hoffer (Lower Austria), Dr Ursula Karnthaler (Vienna), LSD HR Dr Christoph König (Salzburg), LSD OstPhys Dr Elizabeth Kremeier (Vienna), ORGR Dr Claudia Krischka (Burgenland), Dr Anita Luckner-Hornischer (Tyrol), Dr Eva Magnet (Upper Austria), LSD Dr Stefan Meusburger (Upper Austria), LSD Dr Gerhard Olexinski (Carinthia), Dr Robert Sollak (Salzburg), Dr Jana Stirling (Vienna), Dr Josefine Weninger (Burgenland), Dr Marianne Wassermann-Neuhold (Styria)

Members of the vaccination committee of the senior medical corps, the hygienics advisory board and the Ministry of Health, Family and Youth (BMGFJ)
(in alphabethical order) Univ-Prof Dr Franz Allerberger, MR Dr Magdalena Arrouas, StPhys Dr Chrstine Bruns, Univ-Prof Dr Manfred Dierich, MR Dr Wolfgang Ecker, MR Dr Helmut Frizza, Univ-Prof Dr Beatrix Grubeck-Loebenstein, Univ-Lektor Dr Hubert Hartl, Univ-Prof Dr Heidemarie Holzmann, Univ-Prof Dr Hanns Hoffmann, MR Dr JeanPaul Klein, Univ-Prof Dr Cornelia Lass-Flörl, Mag Petra Janda, Univ-Prof Dr Herwig Kollaritsch, Univ-Prof Dr Walter Koller, LSD OStPhys Dr Elzabeth Kremeier, Univ-Prof Dr Michael Kundi, Univ-Prof Dr Michael Kunze, Univ-Prof DDr Egon Marth, Univ-Prof Dr Helmut Mittermayer, Univ-Prof Dr Ingomar Mutz,
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Influenza Pandemic Plan

Univ-Prof Dr Hannes Pichler, Univ-Prof Dr Manfred Rotter, MR Dr Wilhelm Sedlak, Univ-Prof Dr Hans Seyfried, Prof Dr Robert Schlögel, Univ-Prof Dr Gerold Stanek, Univ-Prof Dr Josef Thalhammer, Dr Barbara Tucek, Univ-Prof Dr Agnes WechslerFördös, Univ-Prof Dr Günther Wewalka, Univ-Prof Dr Werner Zenz, MR Dr Maria Woschitz-Merkac, Univ-Prof Dr Franz Zwiauer

Further associates
Univ-Doz Dr Hartmut Huemer (Innsbruck University Medical Faculty), Univ-Prof DDr Armin Prinz (Vienna University Medical Faculty), HR Dr Michael Schönauer (AGES=Austrian Agency for Health and Food Safety), Dr Herbert Tomaso (BMLV = Federal Ministry of Defence)

Thanks are also due to
Prim Dr Norbert Vetter, Univ-Prof DDr Wolfgang Graninger and OA Dr Arno Lechner for their expert advice on the treatment of secondary diseases Director Karl Buresch, Medical Media Association (CliniCum) for permission to copy the CAP synoptical tables OA Dr Hermann Laferl for his expert advice on the triage criteria for hospital admission

Addresses
WHO Pandemic Plan: http://www.who.int/csr/resources/publications/influenza/GIP_2005_5Eweb.pdf National pandemic plans: http://www.who.int/csr/disease/influenza/nationalpandemic/en/ Robert-Koch-Institut/Berlin: http://www.rki.de/cln_049/nn_197444/DE/Content/InfAZ/I/Influenza/Influenzap andemieplan.html?__nnn=true Austrian regional plans: http://www.gesundheitkaernten,at/gesundheitsserverthml/page.asp?MEN_ID=191 http://www.verwaltung.steiermark.at/cms/beitrag/10431178/9752/ http://www.tirol.gv.at/themen/gesundheit/influenza/pandemieplantirol/ http://www.wien.gv.at/gesundheit/sandirektion/influenza/index.html/

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Imprint
Proprietor, Publisher and Editor:
Federal Ministry for Health, Family and Youth (BMGFJ) Radetzkystraße 2 A-1030 Vienna

Concept, Overall Management and Editing:

DDr Reinhild Strauss Head of Dpt. Infectious Diseases, Health Threats and Crisis Management, BMFGJ Mag Ulrich Herzog, CVO Federal Ministry for Health, Family and Youth, Chief Veterinary Officer, BMGFJ

Responsible for the contents:

MedR Dr Hubert Hrabcik General Director of Public Health, Federal Ministry for Health, Family and Youth, BMGFJ

Layout:

Christine Hain Dpt. of Infectious Diseases, Health Threats and Crisis Management, BMGFJ

Printers:

Printed by The Federal Ministry for Health, Family and Youth (BMGFJ)’s printers ISBN 978-3-90-2611-05-5 English translation of the third edition

Contact: reinhild.strauss@bmgfj.gv.at

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An influenza pandemic is defined as the worldwide occurrence of masses of cases and deaths caused by a new influenza subtype. Since avian flu in animals has become endemic the risk for a new influenza pandemic in human has increased dramatically. WHO and the European Commission therefore have urgently asked the member states since years to provide national contingency plans. The aim of this manual is to provide command - control structures with clearly defined competencies of all key players. This will facilitate rapid and efficient crisis management in the case of an influenza pandemic.

The Pandemic Plan can be downloaded from the internet under: www.bmgfj.gv.at

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