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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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Influenza Pandemic Plan

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. Diagnosis aims..........................................................................28


3.2.2. Samples...................................................................................28
3.2.3. Diagnostic methods ...................................................................29
3.2.4. 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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Influenza Pandemic Plan

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

o Provincial implementation concepts (operative plans) which contain


concrete measures for vaccination, medicinal prophylaxis and hospital
provision.

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.

o Expanded crisis committee: representatives of the armed forces, the


police, the ambulance services, the nursing services, health insurances,
the chamber of pharmacists, NGOs,..

• The members of the federal and provincial crisis committees must be on 24-
hour 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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Influenza Pandemic Plan

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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Influenza Pandemic Plan

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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Influenza Pandemic Plan

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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Influenza Pandemic Plan

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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Influenza Pandemic Plan

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, co-
ordination 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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Influenza Pandemic Plan

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

22
Influenza Pandemic Plan

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

23
Influenza Pandemic Plan

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.

24
Influenza Pandemic Plan

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 sub-
types/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

25
Influenza Pandemic Plan

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.

26
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.

27
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

28
Influenza Pandemic Plan

• 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:
ƒ Virus cultivation from sample material of suspected cases of
influenza within the framework of the nationwide influenza
surveillance (Sentinella system)
ƒ Typing and subtyping of cultivated influenza virus stems;
serological fine typing, characterisation of hemagglutinate and
neuraminidase through PCR and sequence analysis
ƒ Close cooperation with the WHO influenza centre
ƒ 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

29
Influenza Pandemic Plan

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

30
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
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-Ehrlich-
Society and the European Respiratory Society; expert communication (Univ-Prof DDr W. Graninger, OA
Dr A. Lechner)
2
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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Influenza Pandemic Plan

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)

32
Influenza Pandemic Plan

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 multi-
layered 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.

33
Influenza Pandemic Plan

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.

34
Influenza Pandemic Plan

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

35
Influenza Pandemic Plan

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

36
Influenza Pandemic Plan

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)

37
Influenza Pandemic Plan

*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.

38
Influenza Pandemic Plan

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

39
Influenza Pandemic Plan

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.

40
Influenza Pandemic Plan

Data for the Influenza


Pandemic Plan

41
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

42
Influenza Pandemic Plan

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.

43
Influenza Pandemic Plan

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.

44
Influenza Pandemic Plan

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

0 100 200 300 400 500 600


cases in 1000

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 2001-
2005 (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).

45
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

*)
standardised rate (standard population = European population)
Sources: BMGFJ – documentation of diagnoses and procedures; ST.AT - population 2001-2005; calculations by GÖG/ÖBIG

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

*)
standardised rate (standard population = European population)
Sources: BMGFJ – documentation of diagnoses and procedures; ST.AT - population 2001-2005; calculations by GÖG/ÖBIG

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

49
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

o Austria keeps abreast of the epidemiological situation in Europe by


exchanging information with other European countries EISS1 and
EUROGROG2

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.

51
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

52
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

53
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

54
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: 30mg once a day


> 15-23kg: 45mg once a day
> 23-40kg: 60mg once a day
> 40kg: 75mg once a 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

55
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

56
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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Influenza Pandemic Plan

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

58
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 so-
called 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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Influenza Pandemic Plan

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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Influenza Pandemic Plan

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, room-
saving 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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Influenza Pandemic Plan

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 human-
human 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 “Core-
Pandemic” 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).

64
Influenza Pandemic Plan

SUPPLEMENT
Appendix 1 -11

65
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,..

67
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

68
Group I Group II Group III
APPENDIX 2:
Influenza Pandemic Plan

Clinically STABLE Clinically ± STABLE Clinically UNSTABLE Clinically UNSTABLE

NO comorbidity ONE comorbidity more than ONE ONE morbidity


NO age restriction Age < 65 comorbidity Age > 65
independent of age

Out-patient out-patient/Hospital patient hospital patients


Therapy I recommended Therapy II recommended 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 Group I Group II Group III

Babies and children up to 3 months Amoxicillin 3x1g p.o. Amoxicillin/Clac 3x1g p.o. Piperacillin/Taz 3x4,5g i.v.
Amoxicillin Cefadroxil 2x2g p.o. Ampicillin/Sulb 3x0,75g p.o.
Cefalexin 3x1g p.o. Bacampicillin 3x0,8g p.o. Cefotaxime
Children from 3 months to 14 years Cefetamet-P. 2x1g p.o. Cefepime 3x2g i.v.
Amoxicillin Cefixime 1x0,4g p.o. Cefpirome
Cefadroxil 50-100 mg/kg 3 ED p.o. Cefpodoxime 2x0,4g p.o. Azithromycin 1x0,5g p.o.
Cefalexin Cefuroxime-A. 2x1g p.o. Clarithromycin 2x0,5g p.o. Ceftriaxone
Cefetamet-P. 20mg/kg 2 ED p.o. Roxithromycin 2x0,3g p.o. Cefodizim 1x2g i.v.
Cefixime 8 mg/kg 1 ED p.o. Telithromycin 1x0,8g p.o. Ertapenem 1x1g i.v.

69
Cefpodoxime 5-12 mg/kg 2 ED p.o.
Cefuroxime-A 20-30 mg/kg 2 ED p.o. Acitromycin 1x0,5g p.o. PLUS
Clarithromycin (1-)2x0,5g p.o. Levofloxacin 1x0,5g p.o.
APPENDIX 3:

Roxithromycin (1-)2x0,3g p.o. Moxifloxacin 1x0,4g p.o. Acitromycin 1x0,5g i.v.


Telithromycin 1x0,8g p.o. Clarithromycin 2x0,5g i.v.
Influenza Pandemic Plan

Acitromycin 10 mg/kg 1 ED p.o.


Clarithromycin 15 mg/kg 2 ED p.o. Amoxicillin/Clac 3x2,2g i.v. Levofloxacin 1x0,5-1g i.v.
Roxithromycin 5mg/kg 1 ED p.o. Ampicillin/Sulb 3x3g i.v. Moxifloxacin 1x0,4g i.v.
Telithromycin from the age of 12 Doxycycline 1x0,2g p.o. Cefamandole
1 ED p.o. Cefotiam 3x2g i.v.
Cefuroxime 3x1,5g i.v.
Cefotaxime 3x2g i.v.
Ceftriaxone
Cefodizim 1x2g i.v.
Ertapenem 1x1g i.v.

Levofloxacin 1x0,5g i.v.


Moxifloxacin 1x0,4g i.v.
Influenza Pandemic Plan

APPENDIX 4:

SAMPLE SHEET FOR HYGIENE FILE


Flu (Influenza)

General Agent Orthomyxoviridae


Sample where agent Respiratory secretion
prevalent
Usual manner of infection Droplet infection, direct or indirect
smear infection
Possible ways of Human to human transmission with
transmission in hospitals droplets, transmission through hands
and objects possible
Inform the authorities No
Duration of subsequent 3-5 days after the outbreak of the
measures illness for adults and up to 7 days for
children
Accommodation If hospitalisation is necessary: single
rooms or cohort isolation
Protective Protective smock Necessary
measures Gloves
Mouth/nose protection Necessary (FFP3 mask with ventile)
Protective goggles Necessary
Protective cap Not necessary
Changing shoes Not necessary
Continuous Disinfecting hands After taking off gloves and mask
Disinfection Disinfecting surfaces 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

Instruments 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
Crockery/dishes Disposable dishes should preferably
be used
Bedlinen and patients’ Pack used bedlinen and patients’
clothing clothing into plastic bags and take to
Final laundry
disinfection Patients’ rooms Wipe with surface disinfectant

Cleaning hospital beds Disinfection within the unit


Waste Waste Waste, particularly paper
disposal handkerchiefs, must be put into thick
plastic bags and disposed of

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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

(m=1, f=2)
Gender

(yes=x)
Pneumonia

(yes=x)
Inpatient

(yes=1, no 2)
Vaccinated

(yes=x)
Death
Antiviral therapy
Amantadine =1
Neuraminidase inhibitors =2
Patient Nr.

DOCTOR’S CODE

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Influenza Pandemic Plan

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: clinical case with laboratory confirmation


Probable case: -
Possible case: clinical case with epidemiological connection

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.

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Influenza Pandemic Plan

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 Jean-
Paul 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,

73
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 Wechsler-
Fördös, 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.gesundheit-
kaernten,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/

74
Influenza Pandemic Plan

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

75
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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