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West Nile virus meningoencephalitis imported into Germany.
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MedLine Citation:
PMID:  23017806     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Authors:
Jörg Schultze-Amberger; Petra Emmerich; Stephan Günther; Jonas Schmidt-Chanasit
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Publication Detail:
Type:  Case Reports; Letter    
Journal Detail:
Title:  Emerging infectious diseases     Volume:  18     ISSN:  1080-6059     ISO Abbreviation:  Emerging Infect. Dis.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-28     Completed Date:  2013-02-19     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  9508155     Medline TA:  Emerg Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1698-700     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Viral / blood,  cerebrospinal fluid
Canada
Female
Germany
Humans
Meningoencephalitis / diagnosis*,  virology
Travel*
West Nile Fever / diagnosis*,  virology
West Nile virus / immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Viral
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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Journal Information
Journal ID (nlm-ta): Emerg Infect Dis
Journal ID (iso-abbrev): Emerging Infect. Dis
Journal ID (publisher-id): EID
ISSN: 1080-6040
ISSN: 1080-6059
Publisher: Centers for Disease Control and Prevention
Article Information
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Print publication date: Month: 10 Year: 2012
Volume: 18 Issue: 10
First Page: 1698 Last Page: 1700
PubMed Id: 23017806
ID: 3471623
Publisher Id: 12-0204
DOI: 10.3201/eid1810.120204

West Nile Virus Meningoencephalitis Imported into Germany Alternate Title:West Nile Meningoencephalitis, Germany
Jörg Schultze-Amberger1
Petra Emmerich1
Stephan Günther
Jonas Schmidt-Chanasit
Klinikum Ernst von Bergmann, Potsdam, Germany (J. Schultze-Amberger);
and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (P. Emmerich, S. Günther, J. Schmidt-Chanasit)
Correspondence: Address for correspondence: Jonas Schmidt-Chanasit, Bernhard Nocht Institute for Tropical Medicine, Department of Virology, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Bernhard Nocht Strasse 74, D-20359 Hamburg, Germany; email: jonassi@gmx.de

To the Editor: West Nile virus (WNV) is a single-stranded RNA virus in the family Flaviviridae that is transmitted to humans by mosquitoes. Approximately 80% of WNV infections in humans are asymptomatic, whereas ≈20% of infected persons experience fever, often accompanied by a rash. Less than 1% of infections are manifested as neuroinvasive disease, such as meningoencephalitis, polyradiculoneuritis, and polio-like flaccid paralysis (1). WNV is endemic in Africa, southern Asia, and northern Australia, and only sporadic cases or small epidemics are seen in Europe (2). In 1999, WNV emerged in North America. By 2010, ≈1.8 million persons had become infected, with 12,852 reported cases of meningoencephalitis and 1,308 deaths (2). In Europe, the last notable outbreak of WNV infection occurred in Greece in 2010; 197 persons were infected, and 33 died (3). The Czech Republic, Denmark, France, and the Netherlands reported laboratory-confirmed WNV infections in travelers returning from North America (1).

We report a case of WNV meningoencephalitis in a 28-year-old German woman, who sought treatment the emergency department of a hospital in Potsdam, Germany, on September 7, 2011. She had a 3-day history of fever of up to 40°C and mental confusion. Six days before admission, she had returned from a 2-week holiday trip to Ottawa, Ontario, Canada. She had spent most of her time in the city of Ottawa.

The patient’s medical history was unremarkable. She was in a reduced general condition because of a severe encephalitic syndrome characterized by somnolence, meningism, fever, and mental confusion. Laboratory investigations revealed leukocytosis with 15.000 leukocytes/µL (reference range 4,400–11,300 leukocytes/µL) and elevated C-reactive protein of 14.8 mg/L (reference <3 mg/L). Cerebrospinal fluid (CSF) analysis on the day of admission showed pleocytosis, 430 cells/µL (72% granulocytes, 27% lymphocytes. and 1% monocytes); elevated levels for total protein, 1,023 mg/L (reference range 150–450 mg/L); an albumin level of 637 mg/L (normal range 0–350 mg/L); and a moderately elevated level of the albumin quotient of 20 (reference range <6.5). The CSF/serum diagrams demonstrated a moderate disturbance of the blood–CSF barrier and a substantial intrathecal IgM synthesis of 27.6% (6.15 mg/L) but no intrathecal IgA or IgG synthesis. Results of magnetic resonance imaging of the brain were unremarkable. No parenchymal lesions were found.

Antimicrobial drug therapy was initiated with ceftriaxone and ampicillin. Acyclovir was administered empirically for herpes simplex encephalitis until this diagnosis was excluded. Molecular and serologic testing of serum and CSF samples revealed no acute infection with herpesviruses, enteroviruses, alphaviruses, orthobunyaviruses, and arenaviruses or with mycobacteria, Borrelia spp., Toxoplasma gondii, Chlamydia spp., Leptospira spp., and Mycoplasma pneumoniae. CSF and blood cultures were negative for fungi and bacteria, including mycobacteria. An encephalitic syndrome caused by N-methyl-D-aspartate antibodies was also excluded. On the basis of the patient’s travel history, the clinical symptoms, and the initial laboratory findings, WNV infection was suspected. Indirect immunofluorescence assays and virus neutralization tests (VNT) for WNV and other flaviviruses were performed as described (4). IgM and IgG against WNV were detected in serum and in CSF by indirect immunofluorescence assay with an 8-fold (IgM) and 32-fold (IgG) increase in serum titer from day 4 to day 26 (Table). WNV IgG and WNV IgM titers were higher than the titers of antibodies against the other flaviviruses tested (Table), indicating that the antibodies resulted from a WNV infection. The serologic diagnosis was further substantiated by detection of WNV neutralizing antibodies at day 11 (VNT titer 640). The VNT titer further increased to 2,560 on day 26 after onset of disease. Results of reverse transcription PCR were negative for WNV and members of genus Flavivirus in serum and CSF samples taken 4 days after disease onset. Attempts to isolate WNV from serum and CSF samples in cell culture failed as well. The patient recovered slowly and was discharged from the hospital in Potsdam on September 15, 2011. She was then referred to a neurologic rehabilitation center in Berlin and was discharged from there after 2 months with a characterization of restitutio ad integrum (i.e., full recovery, restoration to original condition).

We report a case of WNV infection imported into Germany that was unambiguously confirmed by laboratory testing. WNV meningoencephalitis was diagnosed on the basis of strict serologic criteria established by the Centers for Disease Control and Prevention (Atlanta, GA, USA) (5). In 2011, 69 clinical cases of WNV infection were reported from the province of Ontario, although no cases in the city of Ottawa were reported (Public Health Agency of Canada; www.eidgis.com/wnvmonitorca). This imported case adds to these cases and suggests that travelers are at risk, even if they visit only Ottawa. Physicians in Germany should be aware of the risk for WNV infection among travelers returning from Canada, especially during late summer.


Notes

Suggested citation for this article: Schultze-Amberger JD, Emmerich P, Günther S, Schmidt-Chanasit J. West Nile virus meningoencephalitis imported into Germany [letter]. Emerg Infect Dis [Internet]. 2012 Oct [date cited]. http://dx.doi.org/10.3201/eid1810.120204

1These authors contributed equally to this article.

References
1. . ArtsobH, GublerDJ, EnriaDA, MoralesMA, PupoM, BunningML, et al. West Nile Virus in the New World: trends in the spread and proliferation of West Nile virus in the Western Hemisphere.Zoonoses Public Health. Year: 2009;56:357–6910.1111/j.1863-2378.2008.01207.x19486320
2. . KilpatrickAMGlobalization, land use, and the invasion of West Nile virus.Science. Year: 2011;334:323–710.1126/science.120101022021850
3. . DanisK, PapaA, TheocharopoulosG, DougasG, AthanasiouM, DetsisM, et al. Outbreak of West Nile virus infection in Greece, 2010.Emerg Infect Dis. Year: 2011;17:1868–7210.3201/eid1710.11052522000357
4. . TappeD, Schmidt-ChanasitJ, RiesA, ZieglerU, MüllerA, StichARoss River virus infection in a traveller returning from northern Australia.Med Microbiol Immunol (Berl). Year: 2009;198:271–310.1007/s00430-009-0122-919727811
5. . Centers for Disease Control and Prevention Epidemic/epizootic West Nile virus in the United States: guidelines for surveillance, prevention, and control [cited 2012 Aug 4]. http://www.cdc.gov/ncidod/dvbid/westnile/resources/wnv-guidelines-aug-2003.pdf

Tables
[TableWrap ID: T1] Table  Results of indirect immunofluorescence assays performed on serum and CSF samples from patient with suspected WNV infection, Germany, 2011*
Virus used as antigen Ig class Antibody titer in serum
Antibody titer in CSF
Day 4 Day 6 Day 11 Day 26 Day 4 Day 6
WNV IgG 320 1,280 5,120 10,240 20 40
WNV IgM 160 160 1,280 1,280 10 20
SLEV IgG 80 80 1,280 2,560 <10 <10
SLEV IgM 20 20 40 <20 <10 <10
JEV IgG ND <20 ND 1,280 ND <10
JEV IgM ND <20 ND <20 ND <10
DENV IgG ND 80 ND 640 ND <10
DENV IgM ND 20 ND <20 ND <10
YFV IgG ND <20 ND ND ND <10
YFV IgM ND. <20 ND ND ND <10
TBEV IgG ND <20 ND ND ND <10
TBEV IgM ND <20 ND ND ND <10

*CSF, cerebrospinal fluid; WNV, West Nile virus; SLEV, St. Louis encephalitis virus; JEV, Japanese encephalitis virus; ; ND, not done; DENV, dengue virus; YFV, yellow fever virus; TBEV, tick-borne encephalitis virus. Titers <20 for serum and <10 for CSF are considered negative.



Article Categories:
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Article Categories:
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Keywords: Keywords: West Nile virus, arbovirus, Germany, serology, viruses, vector-borne infections.

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