Download - Avian Influenza History
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Avian InfluenzaA disease with a history
World Influenza Outbreaks
1934
Puerto Rico
H1N1
World Influenza Outbreaks
1995
Mexico
H5N2
World Influenza Outbreaks
1997
Hong Kong
H5N1 The potential of spreading H5N1 to humanwas prevented by slaughtering all poultry in Hong Kong in December 1997
World Influenza Outbreaks
2001
Hong Kong
H5N1 H5N1 reemerged again in Hong Kong in multiple genotypes.Controlled, again, by slaughtering all poultry in Hong Kong.
World Influenza Outbreaks
2002
Hong Kong
H5N1 H5N1 reemerged again in Hong Kong in multiple genotypes.Controlled by slaughtering positive flocks and infected poultry stalls in markets.
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Avian InfluenzaA disease with a history
Hong Kong Story
Strategies to attempt to control the emergence of highly pathogenic H5N1 viruses in Hong Kong poultry markets.
Hong Kong Story
Slaughter of infected farms and live poultry markets.
All the poultry in Hong Kong were slaughtered. 1997
2002
Birds in the markets and birds due to go to the markets were slaughtered.
No farms in Hong Kong were shown to be infected. 2001
Serological screening of each truckload of poultry sold from local farms or entering Hong Kong.
Removal of aquatic birds including ducks and geese from the live poultry markets in 1998.
Quail was identified as the poultry species that continued to reintroduce H6N1 and H9N2 viruses into the Hong Kong poultry markets and were banned.
Introduction of one “clean day” per month when all poultry markets are simultaneously empty and are cleaned.
What after Hong Kong Story
These measures successfully removed the different H5N1 influenza virus genotypes from Hong Kong poultry markets.
They have so far not prevented reemergence of H5N1 influenza viruses.
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Avian InfluenzaA disease with a history
What after Hong Kong Story
After the third reintroduction of H5N1/02 influenza virus in Hong Kong, the decision was made to investigate the use of inactivated vaccine to reduce the H5N1 virus load and inhibit the further reemergence of H5N1 genotypes.
H5N2 … The First Use
Inactivated vaccine was successfully used to control the H5N2 outbreak in Mexico in 1995 (Villard and Flores, 1997).
H5N2 … The First Use
We investigated the efficacy of commercially available H5N2 influenza vaccine against H5N1/02 influenza viruses from Hong Kong.
The only commercially available inactivated H5 influenza vaccine is against A/CK/Mexico/232/94 (H5N2).
ASSESSMENT
H5N2 … Immune Response
Amino acid sequence identity between the HA of:A/Ck/Mexico/232/94 (H5N2) A/Ck/Hong Kong/86.3/02 (H5N1)
To evaluate the immune response after single and multiple doses of commercial inactivated H5N2 influenza vaccine.
89.3%
H5N2 … Immune Response
Profile:8-day-old chickens were vaccinated vaccine.We have 3 groups of birds:
1. Vaccinated chickens with single dose of A/CK/Mexico/232/94 (H5N2)
2. Unvaccinated in contact with the vaccinated chickens3. Unvaccinated chickens
H5N2 … Assessment
Investigations:Hemaggtutination inhibition (HI) titers:
1. A/CK/Hidalgo/232/94 (H5N2) 2. A/CK/HK/86.3/02 (H5N1)
After two doses of vaccine, higher levels of prechallenge antibodies were induced that did not increase after virus challenge.
Experiment 1
Profile: Vaccinated group (19)• Primary dose of vaccine at 8 day of age – challenged.
Unvaccinated in contact (10)• Not vaccinated – not challenged
Unvaccinated group (9)• Not vaccinated - challenged
Challenge:Aggressive challenge dose of 10 CLD50 of A/CK/HK/86.3/02 (H5N1).
Immune Response
Mean HI antibody titer
H5N1 (H5N2)
Pre
Vaccinated
Unvaccinated
20 53 100 150
Post Pre Post
Unvaccinated in contact
Deaths And Virus Shedding
0/19 0/19
Trachea Cloaca
Death/total - 3 dpc Virus shedding - 3 dpc
6/19
6/9 0/3 1/3
Vaccinated (19)
Unvaccinated (4)
Unvaccinated in contact 0/10 0/10 1/10
After 2-3 days
Experiment 2
Profile: Vaccinated group (10)• Primary dose of vaccine at 8 day of age, boosted 28 days
later – challenged.Unvaccinated in contact (6)• Not vaccinated – not challenged.
Unvaccinated group (9)• Not vaccinated – challenged.
Challenge:Aggressive challenge dose of 100 CLD50 of A/CK/HK/86.3/02 (H5N1).
Immune Response
Mean HI antibody titer
H5N1 (H5N2)
Pre
Vaccinated (10)
Unvaccinated (4)
333 337 391 257
Post Pre Post
Unvaccinated in contact (6)
Deaths And Virus Shedding
1/10 3/10
Trachea Cloaca
Death/total - 3 dpc Virus shedding - 3 dpc
0/10
9/9 ND ND
Vaccinated (10)
Unvaccinated (4)
Unvaccinated in contact (6) 3/6 3/6 2/6
After 2-3 days
Hi Titer 1/80
Experiment 3
Profile: Vaccinated group (10)• Primary dose of vaccine at 8 day of age, which is boosted
28 days laterUnvaccinated group (4)• Nothing
Challenge:Exposed to birds infected with 100 CLD50 H5N1
Immune Response
Mean HI antibody titer
H5N1 (H5N2)
Pre
Vaccinated
Unvaccinated
282 252 388 326
Post Pre Post
0 0 0 0
Deaths And Virus Shedding
0/10 1/10
Trachea Cloaca
Death/total - 3 dpc Virus shedding - 3 dpc
0/10
3/4 0/1 0/1
Vaccinated (10)
Unvaccinated (4)
CONCLUSION
Conclusion
Thus commercial inactivated oil-emulsion A/CK/Mexico/ 232/94 (H5N2) provides protection against challenge with low doses of A/CK/HK/86.3/02 (H5N1) virus but did not prevent virus shedding, which transmitted to contact birds.
Conclusion
When the severity of challenge was increased in the second experiment, 1 of 10 vaccinated birds died but not in the third experiment.
However, virus shedding in vaccinates in the first experiment was sufficient to infect 50% of unvaccinated contact controls.
Despite high levels of HI antibody, the heavily challenged birds were not fully protected, thus raising the question of lack of genetic similarity between the vaccine and challenge virus.