workshop on west nile virus berlin, 13th -17th of … nile epidemiology:global situation and recent...
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Workshop on West Nile virusBerlin, 13th -17th of February, 2012
West Nile epidemiology:global situation and recent
outbreaks in Europe
Tamás Bakonyi1, Norbert Nowotny2
1 Department of Microbiology and Infectious Diseases, Faculty of Veterinary Science, Szent István University, Budapest, Hungary2Zoonoses and Emerging Infections Group, Clinical Virology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
West Nile epidemiology:global situation and recent outbreaks in Europe
• virology
• transmission cycle
• epidemiology and distribution
– West Nile lineages
– the emergence of WNV in the USA
– the European scenario
West Nile epidemiology: global situation and recent outbreaks in Europe
Virology
• West Nile virus (WNV)
– Flaviviridae, Flavivirus, mosquito-borne group,• Japanese encephalitis virus serocomplex
• +ssRNA genome, ~ 11,000 base
• 3 structural and 7 non-structural proteins
• stem-loop structures at the UTR regions
• icosahedral capsid
• enveloped
• relatively weak resistance (heat, detergents)
• strong antigen
– the E glycoprotein is the neutralizing Ag
– one serotype
– cross-reactions with other flaviviruses
West Nile epidemiology: global situation and recent outbreaks in Europe
5’- -3’
C M E NS1 NS2ANS2B
NS3 NS4ANS4B
NS5
West Nile epidemiology: global situation and recent outbreaks in Europe
Transmission cycle• natural host of WNV are wild birds
– several species are susceptible
• USA: 371 bird species
– frequent subclinical infections
• varying length of viraemia
• varying level of virus titre in the blood (amplifying host)
• transient shedding with faeces and body fluids
– certain species are more vulnerable
• USA: 62% of the WNV positive dead birds were American crows and Blue jays
• main vectors are mosquitoes
– several species are potential carriers
• USA: 62 WNV positive mosquito species reported
• >98% of the positive pools are of Culex spp.
• in Europe the principal vector is usually Culex pipiens
– ornithophillic
– overwinters in adult form
– gradation in late summer and autumn
• the extrinsic period is significantly influenced by the weather
Kilpatrik et al., PloSPath. 2008. 4/6, e10000092
infected mosquitoes
disseminated infection in mosquitoes
transmitting mosquitoes
days after feeding
ratio
West Nile epidemiology: global situation and recent outbreaks in Europe
Transmission cycle• natural host of WNV are wild birds
• main vectors are mosquitoes
• tick are also potential vectors
• several other vertebrates are susceptible hosts
– mammals (humans, horses), reptiles (alligators), amphibians (frogs)
– incidental hosts – the mosquitoes’ choice
– dead-end hosts – viraemia is lower than the mosquito infection threshold
• possible non-vectorial transmission
– iatrogenic – blood transfusion, organ transplantation
– intrauterine, lactogenic – reported in humans
– accidental – necropsy, laboratory infections
– peroral
• scavenger birds – carrion feeding (i.e. craws)
• birds of prey (i.e. goshawks)
• virus shedding by faeces (common coots?)
West Nile epidemiology: global situation and recent outbreaks in Europe
West Nile epidemiology: global situation and recent outbreaks in Europe
Epidemiology and distribution– first isolation: West Nile district of Uganda, 1937
• from a febrile woman
– the most widespread flavivirus
• Africa, Europe, Asia, Australia (Kunjin), North and South America
• WNV lineages
– Two main genetic lineages
• lineage 1: word-wide distributed
– topotype strain: Eg101 (Egypt, 1951)
– three clades (~ geographic distribution)
– virulence – variants
• lineage 2: limited distribution
– topotype strain: B956 (Uganda, 1937)
– Sub-Saharan Africa and Madagascar
– strain Q3574-5 isolated in 1968 from a migrating Barred Warbler (Sylvia nisoria) on Cyprus (Watson et al. 1972)
Lanciotti et al.Virology 298, 96-105 (2002)
West Nile epidemiology: global situation and recent outbreaks in Europe
Epidemiology and distribution
• WNV lineages
– Two main genetic lineages
• lineage 1: word-wide distributed
• lineage 2: limited distribution
– topotype strain: B956 (Uganda, 1937)
– Sub-Saharan Africa and Madagascar
– emergence in central Europe (Hungary) in 2004
– emergence in Russia (Volgograd) in 2007
– differences in virulence!
– Further genetic lineages
• lineage 3: Rabensburg strain
– first isolation in the Czech Republic, from Cx. pipiens
– reisolation in 1999 (Cx. pipiens) and in 2006 (Ae. rossicus)
– no Rabensburg strain associated cases reported in the area
– limited pathogenicity in mice
West Nile epidemiology: global situation and recent outbreaks in Europe
Epidemiology and distribution
• WNV lineages
– Two main genetic lineages
• lineage 1: word-wide distributed
• lineage 2: limited distribution
– Further genetic lineages
• lineage 3: Rabensburg strain
• lineage 4: LEIV-Krnd88-190
– isolated in Russia (Caucasus) in 1998
– isolated from ticks (Dermacentor marginatus)
– virulence is unknown
Lineage 1
Lineage 2
Putative Lineage 3
Putative Lineage 4
1a
1b
West Nile epidemiology: global situation and recent outbreaks in Europe
Epidemiology and distribution
• WNV lineages
– Two main genetic lineages
• lineage 1: word-wide distributed
• lineage 2: limited distribution
– Further genetic lineages
• lineage 3: Rabensburg strain
• lineage 4: LEIV-Krnd88-190 (Lvov et al., 2004)
• lineage 5: Indian isolates (Bondre et al., 2007)
• lineage 6: Malaysian isolate (Scherret et al., 2001)
• lineage 7: Spanish isolate (Vazquez et al., 2010)
Bondre et al., J. Gen. Virol. 88:875-84 (2007)
Vazquez et al., 2010. Emerg Infect Dis., 16.: 549-552.
West Nile epidemiology: global situation and recent outbreaks in Europe
Epidemiology and distribution
• The emergence of WNV in the USA
– New York (Queens, Bronx) – 1999
• encephalitis in humans, horses, dogs and cats
• wild bird mortality
• identification of the agent – WNV lin. 1
• genetic characterisation – close relationship with an isolate from Israel (1998)
• the route of introduction remained unknown
– The virus established itself in the new habitat and quickly spread westwards
WNV Neuroinvasive Disease Incidence, by County, US, 1999
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
N=54
L. Petersen, CDC
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
WNV Neuroinvasive Disease Incidence, by County, US, 2000
N=19
L. Petersen, CDC
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
WNV Neuroinvasive Disease Incidence, by County, US, 2001
N=64
L. Petersen, CDC
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
WNV Neuroinvasive Disease Incidence, by County, US, 2002
N=2946
L. Petersen, CDC
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
WNV Neuroinvasive Disease Incidence, by County, US, 2003
N=2866
L. Petersen, CDC
WNV Neuroinvasive Disease Incidence, by County, US, 2004
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
N=1142
L. Petersen, CDC
WNV Neuroinvasive Disease Incidence, by County, US, 2005
N=1294
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
L. Petersen, CDC
WNV Neuroinvasive Disease Incidence, by County, US, 2006
N=1495
Incidence per million.01-9.99
10-99.99
>=100
Any WNV activity
L. Petersen, CDC
2002
2001
2002
2002 2002
2002
2004
2004
2003
West Nile Virus in Latin America
2004
2003
•2003
2004
2003
2004
2006 ArgentinaL. Petersen, CDC
Human WNV Disease Casesby Week of Onset, United States, 2006*
050
100150200250300350400450500550600
7-Ja
n21
-Jan
4-Fe
b18
-Feb
4-M
ar18
-Mar
1-Apr
15-A
pr29
-Apr
13-M
ay27
-May
10-J
un25
-Jun
8-Ju
l22
-Jul
5-Aug
19-A
ug2-
Sep
16-S
ep30
-Sep
14-O
ct28
-Oct
11-N
ov25
-Nov
9-Dec
23-D
ec
Week ending
# ca
ses
* Reported as of 5/2/2007, courtesy L. Petersen
Reported Human West Nile Virus Casesby Date of Symptom Onset; and Date of First Positive Surveillance Event,
Colorado, 2003
0
10
20
30
40
50
60
70
80
90
100
110
06-jú
n-03
20-jú
n-03
04-jú
l-03
18-jú
l-03
01-a
ug-03
15-a
ug-03
29-a
ug-03
12-sz
ept-0
3
26-sz
ept-0
3
10-o
kt-03
24-o
kt-03
Symptom onset date
No.
of
case
s
Fever(n=2323)Neuroinvasive(n=621)mosquito
human
chicken
bird
horse
Source: John Pape, CO DOH
0
2000
4000
6000
8000
10000
12000
14000
16000
1999 2000 2001 2002 2003 2004 2005 2006
0
500
1000
1500
2000
2500
3000
3500
4000
Equine
Human
Equine and Human WNV NeuroinvasiveDisease Cases, United States, 1999-2006
Total Equine: 24,213 cases
Total Human: 9,906 cases
Eq
uin
e C
ase
Rep
ort
s Hu
man
Case R
epo
rts
Vaccine introduced
Reported WNV Disease Cases in Humans,United States, 1999-2006*
YearTotal
WNNDFever
Other
clinical/
Unspec
Total cases
Deaths
1999 59 3 0 62 7
2000 19 2 0 21 2
2001 64 2 0 66 9
2002 2,946 1,160 50 4,156 284
2003 2,866 6,830 166 9,862 264
2004 1,148 1,269 128 2,539 100
2005 1,309 1,607 99 3,000 119
2006 1,495 2,616 194 4,269 177
Total 9,906 13,489 637 23,975 962
* Reported as of 5/2/2007, courtesy L. Petersen
Clinical manifestation of WNV in the USA
• Asymptomatic (approx. 75%)
• West Nile fever (approx. 25%)
• Neuroinvasive disease (approx. 1/140)
– Encephalitis
– Meningitis
– Flaccid paralysis
Courtesy L. Petersen, CDC
Asymptomatic
1,040,300
Fever
322,800
Fever
13,484
Neuroinvasive,
Non-fatal
8,942
Fatal, 962
Reported
The Hidden EpidemicWNV Infections (n=1.4 million), 1999-2006
Not reported
Courtesy L. Petersen, CDC
WNV epidemiology and distributionThe European scenario
• First detection:– Albania 1958 (serology)
• Virus isolation:– France, Russia, Portugal
Slovakia, Moldavia,Ukraine, Hungary,Romania, Czech Rep.,Italy
• Cases, outbreaks:– 1960’s:
France, Russia, Spain, Romania
– 1970-90’s:Byelorussia, Ukraine, Romania, Czech Republic
Hubalek & Halouzka, 1999
virusisolationcase
seropositivity
Zeller & Schuffenecker, 2004
• 2003, France: horse, magpie
• 2002-2007, Spain: imperial eagle (Aquila adalberti)
• 2006-2007, Germany, Poland: seropositive birds
Rather widespread WNV outbreak in summer 2008 in northern Italy
G. Savini et al., 2008, Eurosurveillance
G. Savini et al., 2008, Eurosurveillance
WNV in Hungary
• Serological studies (1969): wild geese, humans
• Isolation (1970’s): bank vole, yellow-necked mouse
→ no documented clinical case
• 2003:
– Goose encephalitis• Great Plain, middle of August
• 6 week-old goslings, 14% mortality
• seroconversion, PCR positivity
• Lineage 1 WNV strain
– Sporadic human meningitis, encephalitis• Great Plain, end of summer – fall
• seroconversion
• 2004-2005:
– encephalitis cases in birds of prey• Körös-Maros National Park
• goshawk, sparrow-hawk; CNS symptoms, mortality
• Lineage 2 WNV strain!
– sheep encephalitis, death• the virus is > 99% identical with the goshawk strain
• 2007:
– mortality in geese
– horse encephalitis
– mortality in birds of prey (goshawk, red-footed falcon)
– human cases
• 2008
– wild bird, hhorse and human cases
– significant geographic sperad
– emergence in Austria
• 2009 – 2011
– WNV activity in the affected areas in every epidemic season
WNV-cases 2004
WNV-cases 2004-2005
WNV-cases 2004-2005-2007
WNV-cases 2004-2005-2007-2008
WNV-cases 2004-2005-2007-2008-2009
WNV-cases 2004-2005-2007-2008-2009-2010
WNV-cases 2004-2005-2007-2008-2009-2010-2011
WNV situation in 2010 in Europe
WNV situation in 2010 in Europe
• northern Greece– August - October 2010
– a widespread WNV outbreak involving mainly humans
– approx. 250 human cases, 191 neuroinvasive, 32 lethal
– Whole genome sequencing revealed the Hungarian / Austrian lineage 2 WNV causing the outbreak in Greece
– however, with a possibly important aa mutation
• Russia – Volgograd region– in summer / autumn 2010
– a widespread WNV outbreak with ~ 231 reported human cases and 6 deaths
– aetiological virus seems to be identical to the one, which caused the 2007 Volgograd outbreak
– a lineage 2 virus, different from the Hungarian/Austrian/Greek one
Papa et al., Clin. Microbiol. Infect., in press
Histidine→ Proline
WNV situation in 2010 in Europe
• northern Greece
• Russia – Volgograd region
• Romania
– ~ 50 reported human cases
– in 2 human samples a lineage 2 WNV is diagnosed
– practically identical with the Volgograd strain
• Serbia (Novi Sad)
– WNV detection in Cx. pipiens pools
– > 99% identity with the Hungarian / Austrian / Greek strain
Human West Nile Disease cases, Romania 2010[Sirbu et al., Eurosurveillance 16 (2), 13 January 2011]
WNV situation in 2011 in Europe
• Ancona, North-East Italy
– WNV detection in a febrile patient
– partial sequence identification
– > 99% similarity to the Hungarian / Austrian / Greek lineage 2 strain
West Nile epidemiology: global situation and recent outbreaks in Europe
Conclusions
• WNV is a significant human and animal pathogen
• increased WNV activity was observed in Europe since 2008
• exotic (lineage 2) strains emerged and are spreading in the continent
• endemic (lineage 1 and 3) strains are also present
• the virus activity is influenced by the weather
• the circulating strains differ in neurovirulence
→ Diagnostic difficulties
→ Necessity of monitoring and surveillance activity
Acknowledgements:
Jolanta Kolodziejek Zoonoses and Emerging Infections Group, Clinical Virology, Department
Helga Lussy of Pathobiology, University of Veterinary Medicine, Vienna, Austria
Bernhard Seidel Office of Ecology Research and Landscape Assessment, Persenbeug,
Austria
Éva IvanicsKároly Erdélyi Central Veterinary Institute, Budapest, Hungary
Krisztina Ursu
Emöke Ferenczi National Center for Epidemiology, Budapest, Hungary
Orsolya Kutasi Large Animal Clinic, Faculty of Veterinary Science, Szent István
University, Üllő, Hungary
Herbert Weissenböck Institute of Pathology and Forensic Veterinary Medicine, Department
of Pathobiology, University of Veterinary Medicine, Vienna, Austria
Katharina Brugger Institute of Veterinary Public Health, University of Veterinary
Medicine, Vienna, Austria
EDENext and Vectorie EU FP7 projects