Lessons learned from the large scale outbreak of Avian Influenza in Holland 2003, based on the publications of Central Institute Animal Disease Control (CIDC – Lelystad, Holland). �

1. Dutch Avian Influenza outbreak 2003
Lessons to be learned
The information used in this presentation is based upon publications
by the RVV, Central Institute Animal Disease Control
(CIDC – Lelystad, Holland)

2. Part one:
The Avian Influenza virus
 What is Avian Influenza?
 Why is it so dangerous?
 Why is protection not possible?
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3. Avian Influenza characteristics
 256 possible combinations of AI
 Different viruses simultaneously occurred in Asia
 Change of character within one (!!) month
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4. INFLUENZA VIRUS STRUCTURE
Nucleoprotein
Matrix protein
Haemagglutinin
8 RNA
segments
Neuraminidase
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5. GENETIC REASSORTMENT
H10N7
H7N7
H7 N3
New Influenza virus:
Cell 256 POSSIBLE
COMBINATIONS!
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6. VIRUS CHARACTERISTICS
 A/chick/2003-H7N7
 All genes are of avian origin
 IVPI = 2,94
 Sequence at cleavage site:
– P E I P K R R R R.G L F
 H7 closely related with A/mallard/2000 H7N3
 N7 closely related with A/mallard/1999 H10N7
 No additional glycosylation sites
(suggest recent introduction from wild fowl)
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7. WILD BIRD SURVEILLANCE
 In 1999 subtype H10N7
and 2000 subtype H7N3
was isolated from mallard
(Anas platyrhynchos) in the
Netherlands
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8. AI OUTBREAK IN THE NETHERLANDS
 Precursor of the H7N7 virus of
Dutch outbreak 2003 is probably a
re -assorted LPAI viruses that
circulated in waterfowl
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9. Conclusions
Part one
 The most likely course of an outbreak of AI is
contact between livestock and waterfowl
 Infected waterfowl keep flying over livestock area ’s
during the bird track
 Avian Influenza is most likely less mortal under
waterfowl in the first period of the incubation time
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10. Part two
Why was the crises in Holland so intense?
 Where did the outbreak start?
 Why were the results for the Dutch poultry industry
so catastrophic?
 What was the influents of scientific research prior
to the outbreak?
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11. START OF AI OUTBREAK
Friday February, 28 2003:
Strong suspicion of AI on 6 layer farms in
Gelderse Vallei
Signs:
Mortality (> 80%), drop in egg production,
decreased food consumption, swollen
heads, cyanosis, diarrhea and respiratory
problems.
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12. OUTBREAKS VS. FARMS AT RISK
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13. POSSIBLE ROUTE OF ENTRY OF AI VIRUS
Source : Agrarisch Dagblad
– Free range laying hens infected by LP H7N7
variant of wild fowl
– Circulated in one stable of index case indicated
by positive serology in absence of signs in this
stable
– Mutation and selection of HP-variant in chickens
– Clinical signs of AI in other stable of index case
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14. 11 AI outbreaks up to 7 March 2003
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15. LPAI VIRUS THAT
CIRCULATED FOR
SOME TIME?
 nation wide serological
surveillance
 carried out from 7-17
March
Animal Health Service
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16. CONTROL OF AI (1)
March 1 : already stand-still
±20 farms infected
March 4 : infected farms culled
+ pre emptive culling within 1 km
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17. March 25 : culling of buffer regions
(Wageningen en Putten)
March 25 : Beneden Leeuwen (March 30)
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18. CONTROL OF AI (2)
 March 27 : setting up of compartments
 April 1 : culling of all flocks in
protection zones GV
 April 3 : Ospel (Nederweert) (7 April)
 April 4 : 2e Stand-still (till April 10)
 April 10 : Koningsbosch (April 14)
 May 5 : Vernhout (Zundert)
(May 9)
 May 11 : last infected farm culled
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19. Lifting restrictions
 Sentinel birds (10%) on infected farms
 Testing after 3 weeks
 If all sentinel birds negative: lifting of surveillance zone
 Last surveillance zone lifted 22 August
 Export live poultry allowed to EU since
 11 July 2003 from the Netherlands with exclusion of existing
surveillance zones
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20. Scientific influences
 The European scientific world is divided in different groups, with all a
different view on what the best possible solution is on culling animals
 Some look at it from an animal welfare point of view, others are
concentrating on swift crises management, some on have made prior
experiences with AI, others reject the view of other scientists, based
upon their own (mostly narrow) scientific vision
 Fighting AI sometimes looks like an exclusive playground for scientists.
Experts outside this scientific community are left out of the discussion,
including farmers organisations, culling experts, scientists specialised
in the human impact of the crises and scientific newcomers with a
different view from what is discussed between exciting scientific
experts in this field
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21. Conclusions part two:
Why was the crises in Holland so intense?
 Density of poultry in the ‘Gelderse Vallei’ was too high
 Culling capacity too small during the first weeks of the crises
 Contingency plan for birds diseases was outdated and still under construction;
the Dutch stamping out procedures during the crises were therefore based
upon outbreak of pigs diseases, prior to the AI outbreak
 No real corporation between farmers and the government was established,
within the first period of the crises
 Too much influence of experts and scientists. They had all a different view
(mostly based upon scientific laboratory knowledge) on how to handle the
crises. This blocked practical solutions (and the necessary pre investments in
culling equipment) and paralysed the crises team that was responsible for
practical planning and control
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22. Part three
Infectiousness and spreading characteristics
 How was it possible that AI was spread in different
area’s in Holland?
 What was the serologic character of the
spreading in Holland?
 What was the most possible reason for the human
mortal case?
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23. Mortality under animals and bio security
 The first signs of AI occur first after the infectiousness was on its top
three days before mortality under the livestock is visible
 Serologic research starts after the first visible signs of AI and takes
days before the AI conformation; announcing that there is a case of AI
and taking precautionary measures is balanced with the financial
impact for the entire industry and beyond that
 In case of the first outbreak, the first line of defence is entirely
depending on the standard of bio security on the infected farm and the
farms and the chain members, in contact with that farm
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24. EXAMPLE MORTALITY
(flock of 3800)
2000 1934
1500
Flock
number
infectiousness
1000
799
583
500
5 15 80
0
23 24 25 26 27 28
day in Feb.
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25. NUMBER INFECTED FARMS: 241
14
12
Number of infec ted farms
10
8
6
4
2
0
7/3
4/4
2/5
28/2
14/3
21/3
28/3
11/4
18/4
25/4
date (2003)
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26. SEROLOGY IN INFECTED ZONES
16
Total: number
14 133548
12
10
Number x 1000
8
6
4
2
0
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Week
negative pos itive
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27. AVIAN INFLUENZA: RT-PCR
1400
Total number:
1200 6073
1000
Number of samples
800
600
400
200
0
10 12 14 16 18 20 22 24 26 28 30 32 34
Week
negative positive
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28. AVIAN INFLUENZA - VIRUS ISOLATION
140
120
Total number: 702
l aantal 702 : 702
Number of samples
100
80
60
40
20
0
10 12 14 16 18 20 22 24 26 28 30 32 34
week
negative positive
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29. RESULTS SEROLOGAL AI-MONITORING IN
THE INFECTED REGIONS
Status of Virus Number of
Positive H7
farm isolation farms
Infected + 241 5
- 14 14
Pre-emptive 1061 0
¶
Prevalence within farm varies form 9 –100 %
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30. HUMAN CASES
25 20
Conjunctivitis
Start case finding
Influenza A conj.
20
H7 conjunctivitis
Number of infected farms
Start antivirals Farms region 2 (5-day avg)
number of cases
15
Farms region 1 (5-day avg) 10
10
Fatal case
5
0
2
6
3
7
5
9
20
24
28
10
14
18
22
26
30
11
15
19
23
27
13
1 May
16-feb
M. Koopmans et al
RIVM
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31. Conclusions part three:
Infectiousness and spreading characteristics
 AI is highly infective prior to the first mortal cases under the flock
 AI travels light, by dust, people, traffic, ignorance and lack of knowledge
 Bio security is of utter importance for the entire poultry industry. Farmers
therefore must be included within the discussions about AI
 Minor mistakes in the contingency plan definitively lead to major consequences
 The human infection risk is high, especially during serological research on not-
infected farms
 One veterinarian died after such an inspection due to a minor mistake in the
Dutch contingency plan (the only mortal case during the crises in Holland)
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32. Part four:
Speed of spreading, monitoring and culling tactics
 How high was the R h reproduction ratio during the
crises?
 What is the best option: culling inside out (chasing
the virus) or outside in (creating a buffer zone)?
 Was there an Low Path AI strain H7N7 present
before High Path AI infection?
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33. How to stop an
epidemic/ pandemic outbreak
 If the Rh reproduction ratio between flocks is
high, the only option is culling in large numbers
to prevent an epidemic or pandemic outbreak
 If the Rh ratio is in average more than one,
flocks in the entire area within 3 km of an
infected farm must be depopulated as soon as
possible
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34. The speed of spreading
 Immediate action within the first 24 hours is vital to
stop rapid spreading of the AI
 Holland was not prepared: R h reproduction ratio at
the start of the crises was 8,6
 No pre investments in culling capacity was made
before the crises, due to high costs and internal
political/ scientific discussions, coursing only
endless discussions on funding
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35. INFECTION RATE REPRODUCTION RATIO RH BEFORE
AND AFTER THE IMPLEMENTATION OF MEASURES
Gelderse Vallei Limburg
Period A B+C A B+C
0.86
5.0 0.91 2.9
Rh (0.28-
(2.9-8.6) (0.39-2.13) (no CI)
2.68)
95% confidence intervals between brackets
A, before implementation of measures, B and C, after implementation of
measures. Periods B and C were combined, because of non-significant
differences J.A. Stegeman et al. 2003
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36. STOP AN EPIDEMIC
BY STAMPING OUT
R>1
R<1
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37. Culling tactics
 Culling from the centre of the outbreak is essential to catch
up with the spreading of the virus and to reduce the R
factor
 Creating buffer zones is essential to protect non-infected
farms in the area
 Both options must be carried out simultaneously
 Two fully equipped culling crews with sufficient capacity
must be available to carry out this tactic of both inside out
and outside in culling approach
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38. Monitoring
results
 Samples of Low Path AI were found in samples taken from the period
November 2002 till February 2003, prior to the High Path outbreak
 1224 farms were inspected
 27.010 samples IDEXX ELISA were taken
 3 farms were found positive
 The Low Path AI strain found prior to the outbreak was of type H7N3
 This strain was detected in December 2002
 The strain was isolated in an other part of country than were the crises started
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39. Conclusions part four
Speed of spreading, monitoring and culling tactics
 Especially in the first week of the crises, the R h reproduction ratio is extremely
high (in Holland, it was factor 8,6; meaning that one farm infected 8.6; each
other infected farms infecting other farms, and so on, and so on
 All efforts must be put in reducing the R h ratio
 Both culling tactics must take place simultaneously; sufficient equipment must
be available before the outbreak
 Funding for pre investments in culling equipment is necessary; in case the
purchasing process starts after the outbreak is confirmed, the responsible
government pays all the costs and the purchasing prices are not negotiable,
leading to high costs and delivery problems
 Pre monitoring is necessary to notice possible first signs of LP- and HP-AI; in
waterfowl and in livestock
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40. Part five:
Imidiate actions
 What did the Dutch authorities do to stop
the crises?
 Why did the crises team work out of a
mobile crises centre?
 Did it help to prevent a pandemic outbreak?
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41. Immediate actions
(1)
 Stand still on livestock transportation, markets,
etcetera
 Forming crises teams on different levels
 Implementing zoning and transportation protocols
 Hiring contracters
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42. Immediate actions
(2)
Mobile crises centre; ‘Stroe’
 During former animal disease crises, the Dutch authorities successfully
developed a model for a mobile crises management Centre, based
upon the use of a mobile office centre; all participants dealing with
crises management used this centre for their operations
 This centre made an interdisciplinary approach possible to coordinate
and control the crises
 Also major suppliers used this centre for their operations
 The centre was also used for coordinating information management,
accounting, public relations and logistic purposes
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43. Immediate actions
(3)
Control Measures
Stand still
 Reduction of number contacts
(Pre-emptive) culling
 Reduction of infectiousness
– Infected farms should be culled within 24 hours
 Reduction of number of susceptible birds (farms)
– Pre-emptive culling within 48 hours
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44. Immediate actions
(4)
Measures on February 28TH
Stand still
 Nation wide for 72 h
– Ban of movement of live poultry, hatching eggs,
poultry manure,
– Export ban on all export of live poultry and eggs
– Ban on gathering of poultry and other birds
– Obligation to keep poultry inside - ban on free-
range housing
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45. Immediate actions
(5)
Measures on February 28TH
Protection zone with radius of 3 km
– Clinical inspection
 Suspected holding:
– 5 moribund or diseased birds and 20 blood
samples
 No disease:
– 20 trachea swabs + 20 blood samples
 Surveillance zone with radius of 10 km
– Clinical inspection
 of all holdings to be finished before lifting 21 days after
last cleaning and disinfection
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46. Culling
 What culling methods were used?
 Why did they not only use stable gassing but also
the HKI Methods © ?
 What are the major differences between these
culling methods?
 Why was the HCN method not used during the
Dutch crises?
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47. Culling
(1)
 Capacity at start low, later high
(50.000 later 1 million birds per day)
 Methods:
– CO2 gas in containers (by HKI)
– CO2 gas in shed (by gas suppliers)
– CO gas in shed (by gas suppliers)
– CO gas in small containers (by experiment)
– Electrocution machine (by HKI)
– Injection with T61 (small numbers)
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48. Culling
(2)
Stable gassing versus HKI approach
Total amount of animals culled: 1.200 farms; 31,750,000
animals
 Stable gassing:
– 45% of all farms by stable gassing
– 61% of all animals by Co2 stable gassing
– 5 % of all animals by Co stable gassing
 HKI Approach
– 55% of all farms by HKI approach
– 33% of all animals by HKI approach
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49. Culling
(3)
Notes on stable gassing
 Stable gassing as a method can be only used in large stables
 Housing, type of animal, age and amount of animals are crucial for
deploying the most effective and efficient culling method
 In Holland, only 45% of all farms were suitable for stable gassing,
housing 66% of all animals
 Individual culling is by far more complicated than Stable gassing
 Until now, no gas supplier has come up with better ideas to speed up
this culling method to reduce the actual culling time to 10 to 15
minutes, accepting a period of 30 minutes to 3 hours as the best
possible option
 In case of a new large scale outbreak, gas supply will be a limiting
factor, due to shortage of gas trucks to transport the gas to the farms
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50. Culling
(4)
Notes on culling operation
 In order to cull from the inside out (chasing the virus) and
culling outside in (buffering zone) two fully equipped culling
teams are needed
 Only a view machines are needed within the crises area at
the first 24 hours, but a large amount of machines have to
be in stock to catch up after that
 Trained personnel is essential, especially to safe garden
animal welfare aspects during a crises
 No personnel from outside the area should enter an
infected zone without an absolute reason for it. Personnel
should be recruited within the zone and before a possible
crises. Therefore corporation with farmers and the farmers
industry is crucial
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51. Culling
(5)
Notes on capacity
 Speed of operation is not depending on the
capacity of the equipment used, nor on the culling
method
 Speed of operation is basically a matter of proper
organisation and logistics
 Culling operations can easily walk out of hand in
case the logistics fail
 Registration during the culling operation is the
source of future planning
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52. Culling
(6)
Notes on the veterinarian
 Veterinarians are used to work with animals, they are not trained to be
head of operations on a culling sight
 Veterinarians are used to keep livestock alive and not to massive
culling
 Speed of operation is much quicker in case the veterinarian is out of
sight or not available
 During culling operations, animal welfare is only a matter of concern as
long as there is a veterinarian safeguarding it
 One inexperienced or unprepared veterinarian can do more damage to
the culling operation than all other members of the culling team
together
 Veterinarians should be trained about handling animal disease crises,
starting at the university level up to training on the job, to be prepared
better for their role as crises manager during an outbreak
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53. Culling
(7)
HCN is not an option
 HCN is not longer allowed in Holland
 HCN is not an AC approved method listed in the
European legislation HCN is only allowed for
scientific purposes to test culling practices
 HCN is on the list of chemical weapons
 Better methods are available, with less danger for
the people involved in the culling process
 Only a limited amount of experts are licensed to
work with HCN
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54. Culling and the effect on humans
What about respect?
 What about farmers, loosing their entire future?
 What about veterinarians that were not trained for
the job?
 What about the cullers, executing millions of
animals?
 What about animal welfare people, guessing
what’s happening?
 What about the public, with livestock as pets?
 What about the press?
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55. Financial aspects
(1)
The poultry industry
 Direct costs: 376 million Euro (partly paid by the EC)
 Indirect costs: 1 milliard Euro (not insurable under the
Dutch circumstances, due to the current policy of the Dutch
authorities in charge of contingency planning)
 Damaged image of the poultry industry
 Cold shake out with significant losses in market chare,
losses of important parent stocks and grand parent stocks
 Massive losses of jobs
 Blockade on future investments, necessary to implement
new European legislation on housing, animal welfare, bio
security and food quality

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56. Human aspects of culling
(2)
Farmers, cullers and veterinarians
 The industry is the biggest looser in the aftermath
of the crises, especially the farmers and its family
 Special mental care has to be created for farmers,
veterinarians and culling personnel to help digest
their experience
 Professional mental coaches should be part of the
crises teams during an outbreak, to avoid
mistakes coursed by too high pressure due to the
immense responsibilities
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57. Animal welfare aspects of culling
(3)
Animal welfare people
 Animal welfare people should be informed about the
background of the crises, it’s consequences for animal en
human welfare and about the risks of animal diseases in
case of no control
 Animal welfare people should have (limited) access to
information before, during and after a crises to judge
weather all has bin done to avoid unnecessary culling of
animals in conjunction with the human risks and the
financial consequences for the farming industry
 Animal welfare people should be actively involved in
examining the possible culling methods and help to
improve these methods, rather than criticising the
government, farmers and cullers for executing culling
procedures
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58. Virological aspects
 Vaccination
 Transmission
 Diagnostics
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59. Vaccination aspects
(1)
Culling and vaccination
 Stamping out is the only possible option
 No vaccination of life stock during outbreak, only as temperately
procedure in non-infected areas
 Vaccination of life stock protects only 96% of all vaccinated birds
 All vaccinated birds have to be culled (Italy, Mexico, Asia did not cull
vaccinated birds, resulting in new outbreaks of new types of viruses)
 Protection of people: pre-amative vaccination of all people (!!) against
human flue is the best possible protection of those who are in
immediate contact with life stock during the crises
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60. Transmission of AI
(1)
Infection of H7N7 in pigs in Holland
 48 farms with mixed herds that were located within
the protection zones and had infected poultry were
tested for antibodies.
 13 farms: prevalence ranging from 2,2 to 42%.
 No increase in prevalence after re-testing.
 No evidence of efficient transmission among pigs
 H7 haemagglutination inhibition test low specificity.
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61. Transmission of AI
(2)
Transmission in Asia
 Especially in open housing system in Vietnam and
Indonesia (humans, pigs, poultry and ducks living
under the same roof), bio security is likely to faille
 Transmission to other types of birds, elephants
and dogs are recently registered
 Especially young children are in danger
 The first case of human to human transmission is
currently under investigation
 Until now, no change of a transmitted AI virus into
a new human virus is registered
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62. Diagnostic aspects
(1)
 Diagnosis in field difficult lack of characteristic
clinical signs.
– First signs were reduction of food and water
intake
 Early warning system
– Respiratory problems
– Drop egg production
– Increased mortality
 Serological monitoring with emphasis at farms at
risk (a.o. free range farms)
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63. Public Health aspect
Reassortment could result
in human pandemic
 To prevent development of new dangerous strain the chance of simultaneous
infection with HPAI strain H7N7 and human influenza should be minimal
Measures taken:
 Protective clothing, masks and eye protection
 Vaccination against human influenza
 Prophylactic treatment with anti viral drug Tamiflu
 Medical checks of people active at culling
 Several cases of conjunctivitis in people working at culling
 88 people were directly infected, 8,000 people were indirectly infected;
one veterinarian died of pneumonia caused by H7N7
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64. Summery
(1)
 Influenza viruses are to stay in the wild bird population
 Keep poultry separated from wild fowl
 High biosecurity
 Practical contingency plan
 Human- and economic risk management
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65. Summery
(2)
 Compartmentalisation
– targeted surveillance within compartment
 Surveillance of live bird markets
 Targeted vaccination programme
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66. Summery
(3)
 Corporation between farmers, animal health services and officials
 Active involvement of farmers in case of an outbreak
 Sufficient culling capacity to cull the maximum amount of animals
within an area of 3 kilometres within 24 hours after the first
positive AI test results
 Yearly test of the contingency plan with all participants
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67. Conclusions
 HPAI can appear suddenly without detected LPAI infection
 High mortality
 Rapid spread between farms
 Transport
 Persons
 Dust
 Fast culling infected farms essential
 Public health consequences
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