West Nile epidemiology: global situation and recent outbreaks in Europe

Transcription

1 Workshop on West Nile virus Berlin, 13th -17th of February, 2012 West Nile epidemiology: global situation and recent outbreaks in Europe Tamás Bakonyi 1, Norbert Nowotny 2 1 Department of Microbiology and Infectious Diseases, Faculty of Veterinary Science, Szent István University, Budapest, Hungary 2 Zoonoses and Emerging Infections Group, Clinical Virology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria

2 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

3 West Nile epidemiology: global situation and recent outbreaks in Europe Virology West Nile virus(wnv) Flaviviridae, Flavivirus, mosquito-borne group, Japanese encephalitis virus serocomplex +ssrnagenome, ~ 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

4 West Nile epidemiology: global situation and recent outbreaks in Europe C M E NS1 NS2A NS2B NS3 NS4A NS4B NS5

5 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 Culexspp. 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

6 infected mosquitoes ratio days after feeding disseminated infection in mosquitoes transmitting mosquitoes Kilpatrik et al., PloS Path /6, e

7 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?)

8 West Nile epidemiology: global situation and recent outbreaks in Europe

9 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 Q isolated in 1968 from a migrating Barred Warbler (Sylvia nisoria) on Cyprus (Watson et al. 1972)

10 Lanciotti et al. Virology 298, (2002)

11 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

12 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-Krnd isolated in Russia (Caucasus) in 1998 isolated from ticks (Dermacentor marginatus) virulence is unknown

13 1a Lineage 1 1b Lineage 2 Putative Lineage 3 Putative Lineage 4

14 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-Krnd (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)

15 Bondreetal., J. Gen. Virol. 88: (2007)

16 Vazquezetal., EmergInfectDis., 16.:

17 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

18 WNV Neuroinvasive Disease Incidence, by County, US, 1999 N=54 Incidence per million >=100 Any WNV activity L. Petersen, CDC

19 WNV Neuroinvasive Disease Incidence, by County, US, 2000 N=19 Incidence per million >=100 Any WNV activity L. Petersen, CDC

20 WNV Neuroinvasive Disease Incidence, by County, US, 2001 N=64 Incidence per million >=100 Any WNV activity L. Petersen, CDC

21 WNV Neuroinvasive Disease Incidence, by County, US, 2002 N=2946 Incidence per million >=100 Any WNV activity L. Petersen, CDC

22 WNV Neuroinvasive Disease Incidence, by County, US, 2003 N=2866 Incidence per million >=100 Any WNV activity L. Petersen, CDC

23 WNV Neuroinvasive Disease Incidence, by County, US, 2004 N=1142 Incidence per million >=100 Any WNV activity L. Petersen, CDC

24 WNV Neuroinvasive Disease Incidence, by County, US, 2005 N=1294 Incidence per million >=100 Any WNV activity L. Petersen, CDC

25 WNV Neuroinvasive Disease Incidence, by County, US, 2006 N=1495 Incidence per million >=100 Any WNV activity L. Petersen, CDC

26 West Nile Virus in Latin America L. Petersen, CDC 2006 Argentina

27 Human WNV Disease Cases by Week of Onset, United States, 2006* # cases 7-Jan 21-Jan 4-Feb 18-Feb 4-Mar 18-Mar 1-Apr 15-Apr 29-Apr 13-May 27-May 10-Jun 25-Jun 8-Jul 22-Jul 5-Aug 19-Aug 2-Sep 16-Sep 30-Sep 14-Oct 28-Oct 11-Nov 25-Nov 9-Dec 23-Dec * Reported as of 5/2/2007, courtesy L. Petersen Week ending

28 Reported Human West Nile Virus Cases by Date of Symptom Onset; and Date of First Positive Surveillance Event, Colorado, human No. of cases chicken mosquito horse Fever (n=2323) Neuroinvasive (n=621) bird 0 06-jún jún-03 Source: John Pape, CO DOH 04-júl júl aug aug aug szept-03 Symptom onset date 26-szept okt okt-03

29 Equine and Human WNV Neuroinvasive Disease Cases, United States, Total Equine: 24,213 cases Vaccine introduced Equine Case Reports Total Human: 9,906 cases Human Case Reports Equine Human

30 Year Reported WNV Disease Cases in Humans, United States, * Total WNND Fever Other clinical/ Unspec Total cases Deaths ,946 1, , ,866 6, , ,148 1, , ,309 1, , ,495 2, , Total 9,906 13, , * Reported as of 5/2/2007, courtesy L. Petersen

31 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

32 The Hidden Epidemic WNV Infections (n=1.4 million), Not reported Reported Fever 322,800 Fever 13,484 Asymptomatic 1,040,300 Neuroinvasive, Non-fatal 8,942 Fatal, 962 Courtesy L. Petersen, CDC

33 WNV epidemiology and distribution The 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 s: Byelorussia, Ukraine, Romania, Czech Republic Hubalek & Halouzka, 1999 virusisolation case seropositivity

34 Zeller & Schuffenecker, , France: horse, magpie , Spain: imperial eagle (Aquila adalberti) , Germany, Poland: seropositive birds

35 Rather widespread WNV outbreak in summer 2008 in northern Italy G. Saviniet al., 2008, Eurosurveillance

36 G. Savini et al., 2008, Eurosurveillance

37 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

38 : 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

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40 2008 wildbird, hhorseandhumancases significant geographic sperad emergence in Austria WNV activity in the affected areas in every epidemic season

41 WNV-cases 2004

42 WNV-cases

43 WNV-cases

44 WNV-cases

45 WNV-cases

46 WNV-cases

47 WNV-cases

48 WNV situation in 2010 in Europe

49 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

50 Papa et al., Clin. Microbiol. Infect., in press

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52 Histidine Proline

53 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

54 Human West Nile Disease cases, Romania 2010 [Sirbu et al., Eurosurveillance 16 (2), 13 January 2011]

55 WNV situation in 2011in Europe Ancona, North-East Italy WNV detection in a febrile patient partial sequence identification > 99% similarity to the Hungarian / Austrian / Greek lineage 2 strain

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57 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

58 Acknowledgements: JolantaKolodziejek Helga Lussy Bernhard Seidel Éva Ivanics Károly Erdélyi Krisztina Ursu Emöke Ferenczi Orsolya Kutasi Herbert Weissenböck KatharinaBrugger Zoonosesand Emerging Infections Group, Clinical Virology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria Office of Ecology Research and Landscape Assessment, Persenbeug, Austria Central Veterinary Institute, Budapest, Hungary National Center for Epidemiology, Budapest, Hungary Large Animal Clinic, Faculty of Veterinary Science, Szent István University, Üllő, Hungary Institute of Pathology and Forensic Veterinary Medicine, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria Institute of Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria EDENext and Vectorie EU FP7 projects