Development of a quantitative real time PCR assay for the detection ...

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1 Institute for Clinical Microbiology and Immunology,St. Gallen, Switzerland 2 Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm, Sweden 3 University Childrens Hospital, Basel, Switzerland 4 Research Laboratory for Vector-Borne Diseases and National Reference Center for Hantavirus Infections, Queen Astrid Military Hospital, Brussels, Belgium FIRST HUMAN CASE OF HANTA VIRUS INFECTION IN SWITZERLAND Hantavirus: an ignored pandemic in Switzerland ? [Troillet N. Institut Central des Hopitaux Valaisans; Rev Med Suisse Romande 1997 Jan;117(1):3-11] Switzerland - a white spot for hantaviruses ? [Vaheri A. 2000, Haartman Institute, Helsinki, 2000;personal communication] Introduction to Hantaviruses Family Bunyaviridae, Genus Hantavirus, > 20 sero / genotypes, 100 nm, enveloped, negative sense, tri-segmented RNA Worldwide natural reservoir of hantaviruses pathogenic for humans : Rodentia (Order), Muridae (Family) with chronic persistent infection D. Schultze 1 , Å. Lundkvist 2 , U. Blauenstein 3 , P. Heyman 4 Hantavirus serology Serology Day 42 Day 49 Day 146 Day 294 H antavirus IgM (M RL) 5.9 - 0.3 0.3 Hantavirus I gG (M RL) 2.1 - 6.5 2.5 TU LV-IgM (EIA) 0.052 0.47 0.030 - TULV-FRNT - - 160 - Hantavirus foci peroxidase-stained in one well from a tissue culture plate [Niklasson et al. Am. J.Trop.Med.Hyg. 1991, 660-665] Summary First documented case of Hantavirus infection in CH First documented case of acute infection with serotype Tula virus, associated with symptoms uncommon for Hantavirus disease Rare case of Hantavirus infection in context with a rodent bite Awareness of Hantavirus diseases in Switzerland is warranted - Asymptomatic & non-specific mild infections outnumber symptomatic, characteristic infections Two broad clinical presentations : - HFRS - Hemorrhagic Fever with Renal Syndrome, Asia & Europe - Hantavirus Pulmonary Syndrome, North & South America 60'000 to 100'000 hospitalised cases of hantavirus disease / year Prologue August 2000 Kaiseraugst, nearby Basel: a 12 year old boy caught a small rodent, hours later rodent bit the boy Medica l record Out-patient Ho spital stay Follow -up D ay Incident D ay Incident D ay Incident 0 Rodent bite 42 Fever 146 No ne 6-11 Paronychia 42-49 Exanthem a 294 No ne 8 Incisi on of paronychia 49-62 Antibiotic treatment 8-11 Fever 18 Fever 39-41 Fever Case report Clinical features of Hantavirus infections Acknowledgement This work was enabled by cooperation of the authors within the European Network of <Imported> Viral Diseases (http://www.enivd.de) Transmission of Hantaviruses to humans via - - respiratory route (common) - bite (rare) - person-to-person (only Andes virus) Microtus arvalis, known to carry Tula virus 61st Annual Assembly of Swiss Society for Micro-biology, Luzern, 20-21 February 2002 Hantavirus serology indicates a recent infection with TULV: - high IgM index in acute-phase serum samples and a rise of IgG index (Hantavirus ELISA, MRL Diagnostics, USA) - confirmed by seroconversion of IgM in Tula virus (TULV) enzyme immuno assay* Definite diagnosis and serological typing of TULV by: - Tula virus -specific focus reduction neutralisation test (FRNT)** - on convalescent serum, 21 weeks after the rodent bite *Lundkvist Å et al. Virus Research (1996) 45:29-44. **Lundkvist Å et al. Journal of Medical Virology (1997) 53:51-59. The history of Tula virus [Plyusnin A et al. Journ Virol (1994) 68:7833-7839 / [Plyusnin A, Morzunov SP; Microbiology and Immunology (2001) 256: 47-75] 1994 Tula virus in Microtus arvalis, trapped 1987 in Tula, 100 km south of Moskow 1996/7 Tula virus in voles from Czech Rep, Slovakia & Austria 2001 Tula virus -genome sequences in rodents in CH Tula virus considered apathogenic to humans so far 2001 Tula virus -specific antibodies in one serum from a healthy blood donor from the Czech Republic

Transcript of Development of a quantitative real time PCR assay for the detection ...

Page 1: Development of a quantitative real time PCR assay for the detection ...

1 Institute for Clinical Microbiology and Immunology,St. Gallen, Switzerland2 Swedish Institute for Infectious Disease Control, Karolinska Institutet, Stockholm,

Sweden 3 University Childrens Hospital, Basel, Switzerland 4 Research Laboratory for Vector-Borne Diseases and National Reference Center for

Hantavirus Infections, Queen Astrid Military Hospital, Brussels, Belgium

FIRST HUMAN CASE OF HANTA VIRUS INFECTION IN SWITZERLAND

Hantavirus: an ignored pandemic in Switzerland ?[Troillet N. Institut Central des Hopitaux Valaisans; Rev Med Suisse Romande 1997 Jan;117(1):3-11]

Switzerland - a white spot for hantaviruses ?[Vaheri A. 2000, Haartman Institute, Helsinki, 2000;personal communication]

Introduction to HantavirusesFamily Bunyaviridae, Genus Hantavirus, > 20 sero / genotypes, 100 nm, enveloped, negative sense, tri-segmented RNA

Worldwide natural reservoir of hantaviruses pathogenic for humans : Rodentia (Order), Muridae (Family) with chronic persistent infection

D. Schultze 1, Å. Lundkvist 2, U. Blauenstein 3, P. Heyman 4

Hantavirus serology Serology Day 42 Day 49 Day 146 Day 294Hantavirus IgM (MRL) 5.9 - 0.3 0.3Hantavirus IgG (MRL) 2.1 - 6.5 2.5TULV-IgM (EIA) 0.052 0.47 0.030 -TULV-FRNT - - 160 -

Hantavirus foci peroxidase-stained in one well from a tissue culture plate

[Niklasson et al. Am. J.Trop.Med.Hyg. 1991, 660-665]

Summary First documented case of Hantavirus infection in CH

First documented case of acute infection with serotype

Tula virus, associated with symptoms uncommon for Hantavirus disease

Rare case of Hantavirus infection in context with arodent bite

Awareness of Hantavirus diseases in Switzerland iswarranted

- Asymptomatic & non-specific mild infections outnumber symptomatic, characteristic infections Two broad clinical presentations :

- HFRS - Hemorrhagic Fever with Renal Syndrome, Asia & Europe

- Hantavirus Pulmonary Syndrome, North & South America60'000 to 100'000 hospitalised cases of hantavirus disease / year

Prologue

August 2000 Kaiseraugst, nearby Basel: a 12 year old boy caught a small rodent, hours later rodent bit the boy

Medical record

Out-patient Hospital stay Follow-upDay Incident Day Incident Day Incident0 Rodent bite 42 Fever 146 None6-11 Paronychia 42-49 Exanthema 294 None

8 Incision ofparonychia 49-62 Antibiotic

treatment8-11 Fever18 Fever39-41 Fever

Case report

Clinical features of Hantavirus infections

Acknowledgement This work was enabled by cooperation of the authors within the European Network of <Imported> Viral Diseases (http://www.enivd.de)

Transmission of Hantaviruses to humans via- - respiratory route (common) - bite (rare)- person-to-person (only Andes virus)

Microtus arvalis, known to carry Tula virus

61st Annual Assembly of Swiss Society for Micro-biology, Luzern, 20-21 February 2002

Hantavirus serology indicates a recent infection with TULV: - high IgM index in acute-phase serum samples and a rise of IgG

index (Hantavirus ELISA, MRL Diagnostics, USA)- confirmed by seroconversion of IgM in Tula virus (TULV) enzyme

immuno assay* Definite diagnosis and serological typing of TULV by:- Tula virus -specific focus reduction neutralisation test (FRNT)**- on convalescent serum, 21 weeks after the rodent bite

*Lundkvist Å et al. Virus Research (1996) 45:29-44. **Lundkvist Å et al. Journal of Medical Virology (1997) 53:51-59.

The history of Tula virus[Plyusnin A et al. Journ Virol (1994) 68:7833-7839 / [Plyusnin A, Morzunov SP; Microbiology and Immunology (2001) 256: 47-75]

1994 Tula virus in Microtus arvalis, trapped 1987 in Tula, 100 km south of Moskow

1996/7 Tula virus in voles from Czech Rep, Slovakia & Austria

2001 Tula virus -genome sequences in rodents in CH

Tula virus considered apathogenic to humans so far

2001 Tula virus -specific antibodies in one serum from ahealthy blood donor from the Czech Republic