1
Overview of animal outbreaks of AI H5N1 globally since 1997
Ian BrownOIE/FAO/EU Reference Laboratory for AI
VLA-Weybridge, UK
FAO-OIE-WHO Joint Technical Consultation on Avian Influenza at the Human-Animal interface, Verona, Italy 7-9
October, 2008
Epidemiology of avian influenza
• Conventional– wild bird reservoir of LPAI– spread to poultry– some LPAI viruses mutate to HPAI
• H9N2– panzootic
• H5N1 HPAI– completely different
2
HPAI H5N1
H5N1 - early reports
• 1996 progenitor HPAI virus of H5N1 subtype affected geese in Guangdong, China in 1996 (Tang et al., 1998).
• 1997 HPAI H5N1 in poultry in Hong Kong. Virus eliminated by slaughter of all poultry.
• 1999-2002 H5N1 viruses continued to be isolated in Hong Kong in retail poultry markets, waterfowl and with serious outbreaks in poultry markets and farms in 2002 (Sims et al., 2003).
3
H5N1 influenza viruses from ducks in China
Shanghai
1999-2002
2000-2002
1996-2002Hong Kong
1999-2002
Beijing
Guangxi
Fujian
Zhejiang
A/Gs/Guangdong/1/96(H5N1)
Chen et al 2004
December 2003 Jan 2004 H5N1 reported in E Asia
6
Rapid evolution of H5N1 in ducks
• Long term shedding despite antibody
• Retain HPAI characteristics for galliformes
• Antigenic drift
• Increased environmental stability
Sturm Ramirez et al 2006Songserm et al 2006
Silent reservoirs – ducks?• Infection studies in
mallards/Pekin ducks with H5N1
• Some H5N1 HPAI viruses cause:– Acute disease– Systemic infection,
pathology in multiple organs, high virus titres, neurological dysfunction and death
– Efficient transmission between ducks
• Virus shedding via respiratory and intestinal tracts BUT
• H5N1 HPAI virus may circulate subclinically such as proven through serology in recent cases in Germany
7
H5N1 Influenza Viruses Isolated From Live Poultry MarketsH5N1 Influenza Viruses Isolated From Live Poultry MarketsIn Southern China 2004 In Southern China 2004 -- 20052005
0.3%1.8%1.9% 0.5%
Webster et al 2006
Live bird markets may play a significant role in the perpetuation and secondary spread of avian influenza
8
Significant isolations of H5N1 from wild birds in E. Asia
• Hong Kong 2002 numerous species of wild birds Ellis et al 2004
• Japan 2004 crows Mase et al 2005• Mongolia 2005 migratory waterfowl• China 2005 migratory waterfowl lake
Qinghai Chen et al., 2005; Liu et al., 2005
Spread from East Asia to rest of the
Area
9
Epidemiology in Europe
• Five putative phases– Importation risk via captive birds– Spread to Eastern and Central Europe, late
2005– Widespread infection predominantly in wild
birds, February to July 2006– Limited infections in poultry, early 2007– ‘New’ virus introductions from June 2007 to
February 2008
Two mountain hawk eagles smuggled by a man travelling from Bangkok to Brussels in November 2004 were found to be infected with HPAI H5N1 virus genetically close to Thailand strains (clade1)van den Berg et al 2005
10
Importation via captive birds -HPAI H5N1
• Isolation of HPAI H5N1 from captive cage birds in quarantine in England (October 05) ostensibly imported from Taiwan
• Virus closest genetically to a 2005 Chinese duck isolate; clade 2.3 (dk/Fujian/1734/05)
Mechanisms for introduction of HPAI
• Movement of infected poultry• Via poultry products• Indirect mechnical transmission ;
contaminated equipment, vehicles, people.
• Wild birds (Eurasian-lineage H5N1)
12
Mute swans seem to have been good sentinels: role for spread of H5N1 in Europe?
European and other countries HPAI H5N1 reported in swans January –May 2006
Croatia, Germany, Italy, Austria, Bosnia, Greece. Bulgaria, Slovenia, Hungary, Russia, Poland, Serbia, Sweden,France, UK, Azerbaijan, Kazakhstan & Iran
14
Risk categories of H5N1/ HPAI H5 positive birds (proportion of category in positives – proportion
of category in sampled) by country
-1
-0.8
-0.6
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
AT CZ DK FR DE EL HU IT PL SK SL SE UK
Increased migratory risk Intimately associated with poultryMay share farmland May share wetlandMedium Risk Unknown RiskLower Risk
15
Epidemiological curve in wild birds
329 H5N1 HPAI pos 329 H5N1 HPAI pos 20072007CZ (1), DE (318), FR, (7) PL CZ (1), DE (318), FR, (7) PL (3)(3)
•Cas
es p
er w
eek
H5N1 HPAI positive wild birds reported to the CRL for 2006/2007 from EU MS as of 3.4.2008
0
50
100
150
200
250
2006 2007
Weeks
From 1.1. 2006 To 31.12.2007
Results: H5N1 HPAI
16
Conclusions from European episodes• Five putative phases of incursion• Carriage by wild birds but also poultry associated
movement• Primary introduction via wild birds?• Few poultry outbreaks with number of secondary cases• Influence of weather and seasonality• Infection locally of wild birds from outdoor poultry?• Spread to poultry generally as a result of limited
biosecurity over to mammalian species• H5N1 can be controlled in poultry if a
combination of measures are applied BUT – requires strong veterinary infrastructure– cooperation between all stakeholder groups (Vet=PH)– resource intensive
Perspectives of H5N1 HPAI in Africa
• Affected countries – 2006 8– 2007 5– 2008 3 so far!
• None south of equator– NE, W African bias
• Domestic poultry– Many epidemiological
connections within poultry sector likely sources
– Endemicity in some areas• Some wild bird reports
– Role?
17
Phylogeny of HA of H5N1 HPAI
158 viruses
WHO/OIE/FAO H5N1evolution working group, 2008, EID14.
2.1
2.2
2.2
2.22.2
2.2 2.2
1
2.2, 2.5
Various incl. 0, 2.2, 2.3,2.4, 3, 4, 5, 6, 7, 8, 9
2.3
2.2
2.2
2.2
HKSAR0,1,2.3,3,87
2.2
2.2
Distribution of H5 HPAI by genetic clades from Sims & Brown 2008
18
A/turkey/Israel/446/06A/duck/Egypt/2253-3/2006
A/chicken/Egypt/1079-NAMRU3/2007A/chicken/Israel/6308-469/06A/turkey/Israel/6308-420/06
A/chicken/Egypt/1078-NAMRU3/2006A/turkey/Israel/364/06
A/chicken/Nigeria/SO294/2006A/chicken/Nigeria/SO457/2006
A/chicken/Ukraine/27-1-4/06A/chicken/Ukraine/27-9-12/06
A/common pochard/France/06167-2.1/2006A/chicken/Romania/266/06
A/chicken/Turkey/73-2/06A/grey heron/Romania/1266/05
A/turkey/Turkey/1/05A/swan/Azerbaijan/1413-K3-2/06A/cat/Austria/649/06A/mute swan/Austria/216/06A/swan/Slovenia/760/2006
A/swan/Bulgaria/118/06A/red breasted/goose/Greece/128/06
A/mallard/Italy/835/2006A/swan/Greece/119-125/06
A/falcon/Ukraine/598/06A/chicken/Ukraine/6766-1/06
A/Peregrine falcon/Slovakia/Vh246/2006A/swan/Austria/917-7/06A/mute swan/Czech Republic/5170/06A/smew/Slovakia/Vh212/2006A/chicken/Ukraine/598/06A/pigeon/Ukraine/598/06A/pheasant/Ukraine/598/06
A/chicken/Romania/1210/05A/domestic goose/Iraq/812/2006
A/chicken/Turkey/127-20/06A/chicken/Turkey/73-6/06
A/chicken/Turkey/73-13/06A/chicken/Burkina Faso/5346-14/06
A/Guinea fowl/Burkina Faso/5346-26/06A/chicken/Sudan/7279-L4/06
A/chicken/Sudan/1784-7/2006A/chicken/Burkina Faso/5346-11/06
A/chicken/Nigeria/641/2006A/hooded vulture/Burkina Faso/5346-10/0
A/turkey/Ivory Coast/4372-3/2006A/chicken/Burkina Faso/1583-1/07
A/chicken/Ghana/3159-NAMRU3/2007A/goose/Hungary/2823/2/2007A/turkey/England/250/2007A/goose/Hungary/3413/2007
A/whooper swan/Mongolia/3/05A/swan/Romania/1212/05
A/chicken/Romania/1212/05A/red breasted goose/Hungary/6604/06A/chicken/Hungary/6740/06
A/falcon/Germany/R899/2006A/duck/Germany/R603/2006
A/black swan/Germany/R1970-1/06A/turkey/France/06222-1.1/2006
A/common coot/Switzerland/V544/2006A/brown-headed gull/Qinghai/3/05
A/chicken/Crimea/04/2005A/bar-headed goose/Qinghai/5/05A/great black-headed gull/Qinghai/2/05
A/duck/Novosibirsk/56/2005A/chicken/Ukraine/1564/05
A/grebe/Novosibirsk/29/2005A/chicken/Azerbaijan/776-6/06A/chicken/Azerbaijan/776-7/06A/chicken/Krasnodar/123/2006
A/swan/Azerbaijan/1413-K2-2/06A/chicken/Azerbaijan/776-2/06A/chicken/Azerbaijan/776-8/06
A/cygnus cygnus/Iran/754/2006A/Cygnus olor/Italy/742/2006
A/chicken/Moscow/2/2007A/chicken/Afghanistan/1573/47/2006
A/grebe/Tyva/Tyv06-2/2006A/chicken/Korea/IS/2006
A/chicken/Kuwait/689-4a/2007A/chicken/Turkey/72-Gercus-1/2007A/goose/Turkey/21-Bismal-3/2007
A/mute swan/Germany/R1359/07A/black-necked grebe/Germany/R1393/07
A/mute swan/Germany/R1349/07A/chicken/Kuwait/689-14a/2007
A/turkey/Czech Republic/10309-3/07A/turkey/England/2614/2007
A/turkey/Poland/35/07A/mute swan/Czech Republic/10732/07
A/chicken/Romania/10705/07A/turkey/Germany/R1077/06
A/whooper swan/Scotland/1430/06A/mute swan/Poland/709-4/06
A/swan/Bosnia Herzegovina/265-1/06A/chicken/Albania/1079-1/06A/swan/Greece/119-128/06
A/mute swan/Germany/R65/06A/chicken/Azerbaijan/1413-K7-2/06
A/swan/Greece/119-106/06A/Cygnus olor/Astrakhan/Ast05-2-3/2005A/swan/Bosnia Herzegovina/265-2/06
A/buzzard/Denmark/6370/06A/swan/Romania/1496/05
A/common buzzard/Germany/R306/2006A/mute swan/Croatia/1/2005
A/swan/Hungary/3472-1/2006A/chicken/Serbia Montenegro/1077/06A/swan/Serbia Montenegro/1077/06
A/peacock/Denmark/60295/06A/chicken/Romania/170/06
A/chicken/Nigeria/BA209/2006A/chicken/Niger/2130-7/2006
A/chicken/Nigeria/1047-54/2006A/chicken/Nigeria/BA210/2006
A/chicken/Romania/6057-4/06A/goose/Romania/6057-3/06
A/duck/China/E319-2/03A/duck/Hunan/114/05
A/duck/Fujian/1734/05A/q-mesia/England/1219/05
A/q-mesia/England/1267-H/05A/q-mesia /England/1304-sb1/05
8299
86
99
99
79
95
95
83
96
95
91
92
71
82
84
84
84
87
99
88
0.005
2.2.1
2.2
2.3
EMA 1
EMA 2
EMA 3
A/chicken/Krasnodar/123/2006A/swan/Azerbaijan/1413-K2-2/06
A/chicken/Azerbaijan/776-2/06A/chicken/Azerbaijan/776-8/06
A/cygnus cygnus/Iran/754/2006A/Cygnus olor/Italy/742/2006
A/chicken/Moscow/2/2007A/chicken/Afghanistan/1573/47/2006
A/grebe/Tyva/Tyv06-2/2006A/chicken/Korea/IS/2006
A/chicken/Kuwait/689-4a/2007A/chicken/Turkey/72-Gercus-1/2007A/goose/Turkey/21-Bismal-3/2007
A/mute swan/Germany/R1359/07A/black-necked grebe/Germany/R1393/07
A/mute swan/Germany/R1349/07A/chicken/Kuwait/689-14a/2007
A/turkey/Czech Republic/10309-3/07A/turkey/England/2614/2007
A/turkey/Poland/35/07A/mute swan/Czech Republic/10732/07
A/chicken/Romania/10705/07
99
79
91
82
Other genetic characteristics
• Clade 2.2– Most viruses possess PB2 E627K– Five amino acid deletion in NS– Stalk deletion in NA post 1997– Tamiflu sensitive (xH274Y)– Evidence of reassortment between spatially
separated genetic clusters i.e. Africa
19
Pathogenesis in Felidae• Infection studies in domestic
cats fed with infected poultry• Clinical symptoms and death• Contact transmission• Potential longer term
implications for adaptation to mammalian hosts
• Enteric infection- implications for spread?
• ‘Natural infection’ of zoo animals and domestic cats in Thailand
• Europe in vicinity of positive cases in wild birds
Kuiken et al (2004) Science 306, 241Keawcharoen et al (2004) EID 10, 2189-91Rimmelzwaan et al (2006) AmJPath 168Songserm et al (2006) EID 12, 681-683
H5N1 avian influenza in pigs?
• Natural infection– Anecdotal reports– Limited serological evidence in China 2001-3 (Li et al
2004)– Other serology in wider region negative?– Reports from Vietnam and Indonesia but definitive
evidence of infection lacking• Experimental infection studies
– Limited infection URT– Some replication in lungs– No contact transmission– Weak antibody response(Shortridge et al 1998; Choi et al 2005; Lipatov et al 2008)
20
Host range of ‘panzootic’ H5N1
• Aquatic bird reservoir to poultry– Maintenance host: domestic ducks?
• Spill over of HPAI to other hosts– wild birds, role? (Hesterberg et al 2008)– domestic cats (Songserm et al 2006)– mustelids (Klopfleisch et al 2007)– domestic dogs (Songserm et al 2006)
• Virus lacks transmissibility in mammalian species including humans
• Initial interspecies transmission can be influenced by ‘artificial’ mixing of species
21
Global case summary• Globally 60 countries with outbreaks/incidents in
animal populations– Africa
• 11 countries poultry, mammals?– Europe
• 25 countries (12 poultry), mammals– Asian
• 24 countries (23 poultry), mammals
• 2008– 20 countries from three continents– Endemicity in poultry populations– Maintenance in wild birds independent of poultry
unlikely?
Thank you for your attention