Emergence of Novel Influenza Strains
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Transcript of Emergence of Novel Influenza Strains
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THE EMERGENCE OF NOVEL
INFLUENZA STRAINS
Lourens Robberts, PhD, D(ABMM), FCCM
Clinical Microbiologist
Director
2012
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Influenza virus• Types A, B and C
• segmented genome
• ss RNA (single stranded, negative sense)Haemagglutinin
Neuraminidase
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Influenza A virus ecology
Intra-species transmission Inter-species transmission
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Influenza: what does it do?
Influenza in Chicken H5N1 - Kam Tin, 2002Courtesy of Dr H Wong & L Sims, AFCD
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Transmission of influenza viruses
• Transmitted by droplets through the coughing and sneezing of infected persons
• Transmitted by
fomites
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Human influenza: The illness
Normal cells Infected cells
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Human influenza: Epidemics
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Protection from influenza
• Immune response (antibody to the virus haemagglutininand neuraminidase) protects from re-infection
• RNA viruses mutate rapidly
• Change in H and N
• Escape from prior immunity
• Antigenic “drift”
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Influenza Pandemics in History
• In 1957 ‘Asian’ influenza caused more
than 1 million deaths
• In 1968 ‘Hong Kong’ influenza caused
more than 1 million deaths
• In 1918 ‘Spanish’
influenza caused
40 million deaths
2
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Human influenza pandemics
How do the H and / or N glycoproteins change completely ?
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Generating a pandemic virus
• mixing of the genes of two viruses - human and animal
• Genetic reassortment
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The origin of pandemic influenza viruses
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Pandemic influenza• Derived in part or whole
from avian influenza viruses
• Aquatic birds and domestic ducks - the reservoir of influenza viruses
• Subtypes: Haemagglutinins 1-16 Neuraminidase 1-9
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Sialic acid distributes preferentially to the apical domain of cultured epithelial cells
expressing sialic acid predominantly in either α2, 3 or α2, 6 linkage.
Ulloa F , Real F X J Histochem Cytochem 2001;49:501-509
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Avian-humanspecies barrier
N-acetylneuraminic acid-α2,3-galactose linkage on sialyloligosaccharides
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α2-3 α2-6
Ito, T. JV 1998
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• Pigs are susceptible to both human and avian influenza viruses. • A “mixing vessel” for the genesis of pandemic influenza.
Where can avian and human viruses meet,to exchange their genes ?
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How do animal influenza viruses adapt to efficient human – human transmission ?
Pigs: A “mixing vessel”
Reassortment in humans“human mixing vessel”
Reassortment of avian and human influenza virus genes
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The H5N1 incident in 1997
Epidemic Curve of Influenza A (H5N1)
Cases in HKSAR, May - Dec 1997
0
1
2
3
4
5
6
7
15-M
ay
06-J
un
11-J
un
06-J
ul
10-J
ul
03-A
ug
17-A
ug
31-A
ug
12-S
ep
16-S
ep
12-O
ct
26-O
ct
01-N
ov
09-N
ov
16-N
ov
23-N
ov
30-N
ov
07-D
ec
12-D
ec
21-D
ec
26-D
ec
29 D
ec
Dates of onset (Beginning of week)
No
. o
f C
ases
Recovered Deceased
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The H5N1 incident in 1997
• ~ 20% of chicken in live poultry markets carry H5N1 virus• patients with H5N1 disease had contact with live poultry markets
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December 1997• Decision to slaughter all poultry in farms and markets in Hong Kong
• No further human H5N1 cases after the poultry slaughter
Epidemic Curve of Influenza A (H5N1)
Cases in HKSAR, May - Dec 1997
0
1
2
3
4
5
6
7
15-M
ay
06-J
un
11-J
un
06-J
ul
10-J
ul
03-A
ug
17-A
ug
31-A
ug
12-S
ep
16-S
ep
12-O
ct
26-O
ct
01-N
ov
09-N
ov
16-N
ov
23-N
ov
30-N
ov
07-D
ec
12-D
ec
21-D
ec
26-D
ec
29 D
ec
Dates of onset (Beginning of week)
No
. o
f C
ases
Recovered Deceased
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The H5N1 incident in 1997
• What is the source of the human infection?
• How did the virus arise ?
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Humans and Chicken
H5N1 Gs/GD/96-like
H5N1/97
H9N2 G1-like H6N1 W312-like
PB2
PB1PAHA
NP
NA
M
NS
PB2
PB1PA
HA
NP
NA
M
NS
PB2
PB1PA
HA
NP
NA
M
NS
PB2
PB1
PA
HA
NP
NA
M
NS
1997
Guan et al 1999PNAS
Not detectedafter 1997
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The origin of the 1997 H5N1 virus
H9N2H6N1
H5N1 (Gs/Gd)
H5N1
H9N2H6N1
H5N1/97 -like
Amplifier
Mixing vessel
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Evolution of H5N1
viruses: 1996-2004
Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004
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Evolution of H5N1
viruses: 1996-2004
Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004
NS1
M2
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Evolution of H5N1
viruses: 1996-2004
Guan et al PNAS 2002Guan et al PNAS 2004Li et al Nature July 8, 2004
Japan
SE Asia
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2009: pH1N1 (Swine)
Han et al. J Pub Health Epidemiol 2011
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A/California/7/2009 (A/H1N1 component, A H1N1 pdm09) 8/8 *A/Perth/16/2009 (A/H3N2 component) 27/27 *
B/Brisbane/60/2008 (Victoria lineage) 14/26 *
B/Wisconsin/01/2010-like (Yamagata lineage) 12/26
Examples of vaccine components
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