Rabies

Activities in 2009

Rabies

Christine Fehlner-Gardiner

Canadian Food Inspection Agency (CFIA), Ottawa Laboratory Fallowfield (OLF)

Centre of Expertise (CofE) for Rabies

Tel.: (+1-613) 228 6698, Fax: (+1-613) 228 6669

Summary of general activities related to the disease

1.Test(s) in use/or available for the specified disease at your laboratory

The figures below are approximate only, and include the specimens tested at ADRI Lethbridge

Test / For / Specificity / Total
Direct immunofluorescence / Antigen / Lyssavirus specific / 7303
Neuroblastoma culture / Virus isolation / Lyssavirus specific / 4107
Immunohistochemistry / Antigen / Genotype 1 specific / 10
RT-PCR / Genomic RNA – human samples only / Lyssavirus specific / 7
VN(for cooperative projects only) / Antibody / Genotype 1 / 1300
Competitive ELISA(for cooperative projects only) / Antibody / Genotype 1 / 2000

Indirect immunofluorescence with MAb panels

/ Antigen / Virus variant specific / 145

2.Production and distribution of diagnostic reagents

Serum of goats immunised with gradient-purified rabies ribonucleoprotein is labelled with fluorescein isothiocyante.The conjugate produced at OLF is also used at ADRI Lethbridge.OLF and ADRI Lethbridge are the only two laboratories performing rabies diagnostics in Canada.All direct immunofluorescence tests for rabies are conducted using the OLF conjugate.

Monoclonal antibodies (Mabs) to N-, P-, G-, and M-proteins of various Lyssaviruses are produced in cooperation with OLF’sHybridoma unit.The Mabs are used for virus genotype and variant identification.A panel suitable to differentiate between the virus variants occurring in Western Canada is supplied to the rabies lab at ADRI Lethbridge.

The OLF molecular biology group in cooperation with the CofE for Rabies produces specific molecular probesfor PCR and in situ hybridization forrabies virus variant identification and molecular epidemiology.

Reagents supplied to other OIE Member Countries

Polyclonal rabbit antiserum and Mab 5DF12, prepared at the CofE for Rabies were supplied to the Agri-Food and Veterinary Authority of Singapore for use in immunohistochemistry tests for rabies.

Activities specifically related to the mandate
of OIE Reference Laboratories

3.International harmonisation and standardisation of methods for diagnostic testing or the production and testing of vaccines

The OLF rabies laboratory performs quality control on diagnostic rabies conjugate produced at Onderstepoort, South Africa

4.Preparation and supply of international reference standards for diagnostic tests or vaccines

None

5.Research and development of new procedures for diagnosis and control

The OLF rabies laboratory is continuously improving its rabies variant identification capabilities.Variant identification is conducted on all rabies positive submissions.

The laboratory participated in the development of a human adenovirus rabies-glycoprotein recombinant oral vaccine.This new product is presently applied in wildlife rabies control projects in Ontario, Quebec and New Brunswick (2009).The CofE for Rabies participates in monitoring these control efforts through rabies serology and determinations of vaccine stability, and is continuing its research collaboration with the Ontario Ministry of Natural Resources examining the kinetics and duration ofimmune response of target species to this vaccine.

6.Collection, analysis and dissemination of epizootiological data relevant to international disease control

The CofE for Rabies continues to monitor the advancing front of raccoon rabies on the eastern border in a cooperative research project with Quebec authorities.

An OLF Mab panel is used at the Onderstepoort OIE laboratory in South Africa for discriminating between Mokola, Lagos bat, canid and mongoose virus infections.

7.Provision of consultant expertise to OIE or to OIE Members

The CofE for Rabies is participating in a Technical Exchange Program, funded by the Canadian International Development Agency (CIDA), for the development of antibody binding assays for use in serological surveys of Mokola, Lagos bat, canid and mongoose virus infections in South Africa.This project began in 2009 and continues into 2010.

8.Provision of scientific and technical training to personnel from other OIE Members

As part of the Technical Exchange Program, the CofE hosted two visiting scientists from the Onderstepoort OIE laboratory in South Africa for training in ELISA techniques.

9.Provision of diagnostic testing facilities to other OIE Members

None

10.Organisation of international scientific meetings on behalf of OIE or other international bodies

20th International Conference on Rabies in the Americas, Quebec City, Canada, October 2009.Drs. Wandeler, Fehlner-Gardiner and Nadin-Davis were on the National Scientific Committee for this conference; as well Dr. Fehlner-Gardiner is a member of the RITA International Steering Committee.

11.Participation in international scientific collaborative studies

Cooperation with the OIE Reference Laboratory in Onderstepoort and the Allerton Laboratory, KwaZulu Natal, South Africa, as well as with the Marwar Trust in Jodhpur, India, is ongoing.

A WHO Collaborating Centres for Rabies multi-year collaborative study on the development of a therapeutic monoclonal antibody cocktail for rabies is ongoing, with work accomplished thus far published in 2009.

12.Publication and dissemination of information relevant to the work of OIE (including list of scientific publications, internet publishing activities, presentations at international conferences)

Presentations at international conferences and meetings

20th International Conference on Rabies in the Americas, Quebec City, Canada, October 2009:

Dr. Pamela Hamill:

  • “Rabies in Canada – 2007 and 2008”

Dr. Susan Nadin-Davis:

  • “Use of DNA bar-coding methods to improve knowledge of bat rabies epidemiology in Canada”

Dr. Alex Wandeler:

  • Keynote speaker at the workshop on “Control of canine rabies: Sharing experiences South to South”.

Scientific publications in peer-reviewed journals

Safety studies on an adenovirus recombinant vaccine for rabies (AdRG1.3-ONRAB) in target and non-target species.Knowles MK, Nadin-Davis SA, Sheen M, Rosatte R, Mueller R, Beresford A. Vaccine. 2009 Nov 5;27(47):6619-26.

Development of real-time reverse transcriptase polymerase chain reaction methods for human rabies diagnosis.Nadin-Davis SA, Sheen M, Wandeler AI.J Med Virol. 2009 Aug;81(8):1484-97.

Molecular characterization of the complete genome of a street rabies virus isolated in China.Ming P, Du J, Tang Q, Yan J, Nadin-Davis SA, Li H, Tao X, Huang Y, Hu R, Liang G.Virus Res. 2009 Jul;143(1):6-14.

In vitro and in vivo genetic stability studies of a human adenovirus type 5 recombinant rabies glycoprotein vaccine (ONRAB).Knowles MK, Roberts D, Craig S, Sheen M, Nadin-Davis SA, Wandeler AI.Vaccine. 2009 May 5;27(20):2662-8. Epub 2009 Mar 4.

Detection of polyoma and corona viruses in bats of Canada.Misra V, Dumonceaux T, Dubois J, Willis C, Nadin-Davis S, Severini A, Wandeler A, Lindsay R, Artsob H.J Gen Virol. 2009 Aug;90(Pt 8):2015-22.

Mokola virus involved in a human contact (South Africa).Sabeta C, Blumberg L, Miyen J, Mohale D, Shumba W, Wandeler A.FEMS Immunol Med Microbiol. 2009 Sep 8. [Epub ahead of print]

Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs.van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, Schutten M, Osterhaus AD, Majoie CB, Aronica E, Fehlner-Gardiner C, Wandeler AI, Kager PA.PLoS Negl Trop Dis. 2009 Jul 28;3(7):e428.

The control of raccoon rabies in Ontario Canada: proactive and reactive tactics, 1994-2007.Rosatte RC, Donovan D, Allan M, Bruce L, Buchanan T, Sobey K, Stevenson B, Gibson M, MacDonald T, Whalen M, Davies JC, Muldoon F, Wandeler A.J Wildl Dis. 2009 Jul;45(3):772-84.

Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans.Müller T, Dietzschold B, Ertl H, Fooks AR, Freuling C, Fehlner-Gardiner C, Kliemt J, Meslin FX, Rupprecht CE, Tordo N, Wandeler AI, Kieny MP.PLoS Negl Trop Dis. 2009 Nov 3;3(11):e542.

Other communications – Co-authored presentations at international meetings

20th International Conference on Rabies in the Americas, Quebec City, Canada, October 2009:

Dr. Christine Fehlner-Gardiner:

  • “Field Performance of ONRAB and RABORAL V-RG oral vaccines in raccoons and striped skunks in New Brunswick, Canada and Maine, United States of America”, J. Badcock, presenter
  • “G glycoprotein amino acid residues required for RAB1 neutralization are conserved in rabies virus street isolates”, G. Babcock, presenter
  • “Le contrôle de la rage du raton laveur au Québec : évaluation du succès des operations d’épandages d’appâts vaccinaux ONRAB®, Part I”, J. Mainguy, presenter
  • “Le contrôle de la rage du raton laveur au Québec : évaluation du succès des opérations d’épandage d’appâts vaccinaux ONRAB®, Part II”, G. Séguin, presenter
  • “Aerial distribution of ONRAB® baits as a tactic to control rabies in raccoons and striped skunks in Ontario, Canada”, D. Donovan, presenter

Dr. Susan Nadin-Davis:

  • “Human antibody responses to dog and bat rabies with the Milwaukee Protocol”, R. Willoughby, presenter.
  • “ONRAB surveillance”, C. Kyle, presenter
  • “Epidemiology and sequential analysis of skunk associated rabies within the Midwestern United States”, R. Davis, presenter

13.Inscription of diagnostic kits on the OIE Register

i)Did you participate in expert panels for the validation of candidate kits forinscription on the OIE Register? If yes, for which kits?

No

ii)Did you submit to the OIE candidate kits for inscriptionon the OIE Register? If yes, for which kits?

No

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Annual reports of OIE Reference Laboratories and Collaborating Centres, 20091