Istituto Zooprofilattico Sperimentale delle Venezie
Italian health authority and research organization for animal health and food safety
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National reference centre / FAO reference centre for rabies

National reference laboratory / FAO reference centre for rabies

IZSVe has been active in rabies control since 1977, when a Europe-wide WHO Programme for Rabies Surveillance was established (http://www.who-rabies-bulletin.org/). The Centre gained extensive experience in the oral vaccination of foxes, which was carried out for the first time in Italy in 1984, alongside laboratory rabies diagnosis.

IZSVe was designated by the Italian Ministry of Health as the National reference centre for rabies in May 2002 and appointed as an United Nations FAO Reference Centre for rabies in December 2012. The Centre has been authorized by the OIE/WHO (1995), DEFRA (UK) (1999) and, more recently, by the EU (decision 2001/296/EC) to test the effectiveness of rabies vaccination in domestic carnivores by in vitro antibody testing.

IZSVe is accredited according to 17025 ISO standards. All testing is performed according to international guidelines (OIE, WHO). In addition, the following tests have been officially accredited by “Accredia”, the Italian National Accreditation Body:

  • Fluorescent antibody test (FAT)
  • Rapid tissue culture infection test (RTCIT)
  • Fluorescent antibody virus neutralisation test (FAVN)

Activities and servicesEpidemiological situationProjects and collaborationsPublicationsContacts

Activities and services

The institutional activities carried out by the FAO and National Reference centre are listed below:

  • rabies diagnosis and surveillance in wild and domestic animals
  • rabies antibody titration in animals and humans
  • characterization of rabies isolates
  • confirmatory diagnoses made by other laboratories
  • assistance and information to the Ministry of Health regarding rabies control and prevention in animals and humans, as well as regulatory aspects
  • data collection at the national level and for the WHO Rabies Bulletin Europe
  • preparation of programmes of oral rabies vaccination of red foxes
  • monitoring of oral rabies vaccination campaigns in the red fox population
  • standardization of laboratory tests among the regional rabies laboratories and organization of national interlaboratory trials for rabies diagnosis
  • participation in international interlaboratory trials for rabies diagnosis and antibody titration
  • collaboration with other EU or international reference centres
  • national and international training and education sessions dedicated to laboratory staff and veterinary practitioners
  • collaboration with first aid units and infectious diseases departments for rabies diagnosis and epidemiological investigations related to human exposure and suspected cases
  • research activity in the field of rabies epidemiology and control in wildlife, rabies virus characterization, rabies virus dynamics
  • international collaboration in the framework of EU projects

FAO Reference Centre mandate of technical assistance to FAO beneficiary countries

  • Confirmation of rabies diagnosis in accordance with international recommended diagnostic protocols (WHO-OIE)
  • Collaboration on design and implementation of rabies surveillance programmes and vaccine efficacy monitoring programmes
  • Collaboration in research activities
  • Support to FAO activities for rabies prevention and control, including active participation in World Rabies Day (http://rabiesalliance.org/world-rabies-day/)
  • Contribution to improvement and harmonization of laboratory diagnostic capacities, including supply of reference materials and organization of interlaboratory proficiency testing, if necessary
  • Dissemination of information on innovative vaccines or new vaccination strategies and development of new diagnostic tools
  • Contribution to ecological studies on rabies wild and domestic reservoirs

Diagnostic capabilities
             

  • Fluorescent antibody test (FAT)
  • One-Step Reverse Transcriptase -Polymerase Chain Reaction (One –Step RT-PCR)
  • One-Step Real-Time RT-PCR (One-Step rRT-PCR)
  • Sanger sequencing and pyrosequencing
  • Rabies tissue culture infection test (RTCIT)
  • Direct Rapid Immunohistochemical test (dRIT)
  • Sandwich ELISA for antigen detection (under development and evaluation, to be used as screening test in limited laboratory conditions)
  • Rapid chromatographic immunoassay for antigen detection
  • Fluorescent antibody virus neutralization test (FAVN)
  • Rapid fluorescent focus inhibition test (RFFIT)
  • Vaccine bait titration
  • Tetracycline determination on fox teeth and jaws

Epidemiological situation

Italy has recently regained the status of a terrestrial rabies-free country. A national rabies surveillance programme and preventive oral rabies vaccination campaigns targeting the red fox population are implemented on a regular basis.

The north-eastern territories of Italy were affected by rabies in the 1970s and 1980s, as well as between 1991-1995. More recently, an outbreak occured between the end of 2008 and early 2011. Italy regained its rabies-free status in February 2013, with the last case being detected in February 2011. During the 2008-2011 epidemic, a total of 287 rabies cases were confirmed in animals, but no associated human cases were recorded. Infections predominantly affected the red fox population, with occasional spill-overs into other wild species and domestic animals.

The risk of rabies re-introduction into Italy from the bordering areas has long been recognised. Molecular studies related to the 2008-2011 Italian rabies circulation in red foxes revealed that, as with previous rabies epidemics, the latest Italian epidemic had been linked to the epidemiological situation in the adjacent regions. Two viral genetic groups were identified (Italy-1 and Italy-2), both belonging to the Western European clade. Phylogenetic and phylogeographic analyses also revealed that both groups had been circulating in the Western Balkans and Slovenia in previous years and were only later introduced into Italy (Fusaro et al., 2013).

The new epidemiological evidence prompted the introduction of an emergency programme of oral vaccination of foxes according to European guidelines, mandatory vaccination of domestic dogs and heightened disease surveillance by veterinary authorities in wild and domestic animals in affected areas. At the same time, officials initiated regional public health campaigns to increase awareness of both human and animal health risks.

The reference centre gathers epidemiological data, which is transmitted to the national authorities and to the WHO Collaboration Centre for Rabies Surveillance, available at http://www.who-rabies-bulletin.org/.

Projects and collaborations

IDENTIFY Project (OSRO/INT/902/USA)

Technical assistance within the IDENTIFY Project (OSRO/INT/902/USA) to strengthen diagnostic capacity on pathogens and emerging zoonoses in high risk areas (Rabies) under FAO LoA 2013 (n.51007).

Africa Rabies Subnetwork RESOLAB-AO/AC- FAO ECTAD Bamako collaboration

Since December 2010, scientific and technical expertise was provided to the RESOLAB rabies sub-network, which includes twenty three national veterinary laboratories divided into two regional areas: a) RESOLAB-Central Africa (Cameroon, Central African Republic, Chad, Congo, the Democratic Republic of Congo DRC, Equatorial Guinea, and Gabon) and b) RESOLAB-Western Africa (Benin, Burkina Faso, Cape Verde, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Niger, Nigeria, Sierra Leone, Senegal, Sao Tome et Principe, the Gambia and Togo).

Main activities include:

More information is available on the website: http://www.fao-ectad-bamako.org/fr/-Rabies-Sub-Network-

PREDEMICS project (2011-2016)

PREDEMICS project (2011-2016), funded by the European Community’s Seventh Framework Programme (FP7/2007-2013), aims at providing “Preparedness, Prediction and Prevention of Emerging Zoonotic Viruses with Pandemic Potential using Multidisciplinary Approaches”. Emerging infectious diseases have been increasingly recognized over time and represent a persistent global threat. Most of the emerging infectious diseases of humans are zoonotic and the possibility of RNA viruses emerging as major agents of human disease appears almost limitless. Their impact on human, domestic and wild animal health is also likely to be underestimated. Therefore, there is a need to understand factors involved in emergence of human pathogens for improved prediction of the risks of their emergence and pandemic potential. Link: http://predemics.biomedtrain.eu/cms/default.aspx

PREDEMICS activities:

  • An MSc student from Uganda University was hosted by the RC for three months to perform phylogenetic analysis on animal rabies cases collected in Uganda.
  • An evaluation of the genetic and spatial structure of the fox population in northern Italy and of the association between rabies and CDV infections and the genetic characteristics of the fox population was conducted through a microsatellite analysis.
  • A detailed evolutionary analysis of RABVs circulating in north-eastern Italy beween the 2008-2011 rabies epidemic was performed. Sequences were obtained for the hyper-variable region of the nucleoprotein gene, the complete glycoprotein gene and the intergenetic region G-L from 113 selected rabies cases. Two viral genetic groups were identified, both of which had been circulating in the Western Balkans and Slovenia in previous years (Fusaro et al., 2013)

PAZA (EUROPEAID/128304/C/SER/AL)

Within the framework of the PAZA (EUROPEAID/128304/C/SER/AL), personnel of the ISUV (State Veterinary Institute) in Tirana (Albania) were trained on rabies diagnosis and an evaluation of facilities and equipment; oral rabies vaccination program and rabies surveillance was carried out.

Better Training for Safer Food

Better Training for Safer Food, funded by DG-SANCO. Training course to improve prevention and control of rabies in North Africa

  • February 28th –March 1st IZSVe, Legnaro, Italy. Twenty-one participants from four countries of the Maghreb region: Algeria, Mauritania, Morocco and Tunisia.
  • September 30th– October 4th 2012, Nouakchott, Mauritania
  • December 17th – 20th 2012, Tunis, Tunisia.

EFSA AHAW Panel - EFSA Panel on Animal Health and Welfare

Participation in the EFSA AHAW Panel – EFSA Panel on Animal Health and Welfare. “Scientific Opinion on Review of the European Union Summary Report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks—Terms of reference 2 to 7”. The Scientific Opinion highlighted how key issues relevant to data collection are harmonized throughout the EU and Europe, in conformity with relevant legislation. This information is submitted voluntarily by the participating countries and collated by the WHO Collaborating Centre for Rabies Surveillance and Research, which makes the information available through a database (http://www.who-rabiesbulletin.org/Queries/Surveillance.aspx). The database provides up-to-date information by country, animal category (domestic and wildlife) and animals tested negative.

Publications

Chapters

  • De Benedictis, P., & De Battisti, C. (2014). Demonstration of Lyssavirus Nucleic Acids by Pyrosequencing. In In C. Rupprecht, & T. Nagarajan (Eds.), Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention Elsevier edn (pp. 205-217)
  • De Benedictis, P., & De Battisti, C. (2014). Genetic Characterization via Pyrosequencing. In In C. Rupprecht, & T. Nagarajan (Eds.), Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention Elsevier edn (pp. 107-116)

Papers

  • Aiello, R., Zecchin, B., Caenazzo, S.T., Cattoli, G., & Benedictis, P. (2016). Disinfection protocols for necropsy equipment in rabies laboratories: safety of personnel and diagnostic outcome. 234, 75-79. Journal of virological methods. Published by Elsevier B.VApr 15 doi:S0166-0934(15)30123-3
  • De Benedictis, P., Minola, A., Rota Nodari, E., Aiello, R., Zecchin, B., Salomoni, A., Foglierini, M., Agatic, G., Vanzetta, F., Lavenir, R., Lepelletier, A., Bentley, E., Weiss, R., Cattoli, G., Capua, I., Sallusto, F., Wright, E., Lanzavecchia, A., Bourhy, H., & Corti, D. (2016). Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. 8, 407-421. EMBO molecular medicine, Humabs BioMed SA Published under the terms of the CC BY 4.0 licenseMar 18 doi:e201505986
  • Eggerbauer, E., de Benedictis, P., Hoffmann, B., Mettenleiter, T.C., Schlottau, K., Ngoepe, E.C., Sabeta, C.T., Freuling, C.M., & Muller, T. (2016). Evaluation of Six Commercially Available Rapid Immunochromatographic Tests for the Diagnosis of Rabies in Brain Material. 10, e0004776. PLoS neglected tropical diseases, Jun 23 doi:10.1371/journal.pntd.0004776.
  • Rota Nodari, E., Alonso, S., Mancin, M., De Nardi, M., Hudson-Cooke, S., Veggiato, C., Cattoli, G., & De Benedictis, P. (2016). Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy. Zoonoses and public health, Blackwell Verlag GmbHMay 6 doi:10.1111/zph.12268.
  • Wasniewski, M., Almeida, I., Baur, A., Bedekovic, T., Boncea, D., Chaves, L.B., David, D., De Benedictis, P., Dobrostana, M., Giraud, P., Hostnik, P., Jaceviciene, I., Kenklies, S., Konig, M., Mahar, K., Mojzis, M., Moore, S., Mrenoski, S., Muller, T., Ngoepe, E., Nishimura, M., Nokireki, T., Pejovic, N., Smreczak, M., Strandbygaard, B., Wodak, E., & Cliquet, F. (2016). First international collaborative study to evaluate rabies antibody detection method for use in monitoring the effectiveness of oral vaccination programmes in fox and raccoon dog in Europe. 238, 77-85. Journal of virological methods, Elsevier B.VOct 14 doi:S0166-0934(16)30340-8
  • Cliquet, F., Picard-Meyer, E., Mojzis, M., Dirbakova, Z., Muizniece, Z., Jaceviciene, I., Mutinelli, F., Matulova, M., Frolichova,J., Rychlik, I., & Celer, V. (2015). In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife. PLoS One. Oct 28;10(10):e0141537. doi: 10.1371/journal.pone.0141537.
  • De Benedictis, P., De Battisti, C., Marciano, S., Mutinelli, F., Capua, I., & Cattoli, G. (2013). Pyrosequencing of the rabies virus glycoprotein gene to demonstrate absence of vaccine-associated rabies cases following oral vaccination. 195 (3), 388-90. The Veterinary Journal, July 2012 doi:http://dx.doi.org/10.1016/j.tvjl.2012.06.030
  • Fusaro, A., Monne, I., Salomoni, A., Angot, A., Trolese, M., Ferrè, N., Mutinelli, F., Holmes, E.C., Capua, I., Lemey, P., Cattoli, G., & De Benedictis, P. (2013). The introduction of fox rabies into Italy (2008-2011) was due to two viral genetic groups with distinct phylogeographic patterns. 17C, 202-209. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, Elsevier B.VApr 19 doi:10.1016/j.meegid.2013.03.051; 10.1016/j.meegid.2013.03.051
  • Nouvellet, P., Donnelly, C.A., De Nardi, M., Rhodes, C.J., De Benedictis, P., Citterio, C., Obber, F., Lorenzetto, M., Pozza, M.D., Cauchemez, S., & Cattoli, G. (2013). Rabies and canine distemper virus epidemics in the red fox population of northern Italy (2006-2010). 8, e61588. PloS one, Apr 22 doi:10.1371/journal.pone.0061588; 10.1371/journal.pone.0061588
  • Robardet, E., Andrieu, S., Rasmussen, T.B., Dobrostana, M., Horton, D.L., Hostnik, P., Jaceviciene, I., Juhasz, T., Müller, T., Mutinelli, F., Servat, A., Smreczak, M., Vanek, E., Vázquez-Morón, S., & Cliquet, F. (2013). Comparative assay of fluorescent antibody test results among twelve European National Reference Laboratories using various anti-rabies conjugates. J Virol Methods. Jul;191(1):88-94. doi: 10.1016/j.jviromet.2013.03.027.
  • De Benedictis, P., Perboni, G., Gentili, C., Gaetti, L., Zaffanella, F., Mutinelli, F., Capua, I., & Cattoli, G. (2012). Fatal case of human rabies imported to Italy from India highlights the importance of adequate post-exposure prophylaxis, October 2011. 17, pii 20168. Eurosurveillance, 10 May 2012 (epub)
  • De Benedictis, P., Mancin, M., Cattoli, G., Capua, I., & Terrregino, C. (2012). Serological methods used for rabies post vaccination surveys: An analysis. 30, 5611-5615. Vaccine, 8/17 doi:http://dx.doi.org/10.1016/j.vaccine.2012.06.089
  • Morosetti, G., Stifter, K., Trevisiol, K., Mutinelli, F., Bonfanti, L., De Benedictis, P., Capello, K., Piffer, C., Fugatti, A., Lombardo, D., Zambotto, P., & Marangon, S. (2012). Management of rabies emergence in 2010 in the autonomous province of Bolzano (Italy): an overview. 16, e457. International Journal of Infectious Diseases, Elsevier doi:10.1016/j.ijid.2012.05.656
  • Capello, K., Mulatti, P., Comin, A., Gagliazzo, L., Guberti, V., Citterio, C., De Benedictis, P., Lorenzetto, M., Costanzi, C., Vio, P., Zambotto, P., Ferri, G., Mutinelli, F., Bonfanti, L., & Marangon, S. (2011). Impact of emergency oral rabies vaccination of foxes in northeastern Italy, 28 December 2009-20 January 2010: preliminary evaluation. 15, 19617. Euro Surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin, 15 July 2011
  • De Benedictis, P., De Battisti, C., Dacheux, L., Marciano, S., Ormelli, S., Salomoni, A., Tiozzo Caenazzo, S., Lepelletier, A., Bourhy, H., Capua, I., & Cattoli, G. (2011). Lyssavirus Detection and Typing Using Pyrosequencing. 49, 1932-1938. Journal of Clinical Microbiology, American Society for Microbiology May 2011 doi:10.1128/JCM.02015-10
  • De Benedictis, P., Sow, A., Fusaro, A., Veggiato, C., Talbi, C., Kabore, A., Dundon, W.G., Bourhy, H., & Capua, I. (2010). Phylogenetic Analysis of Rabies Viruses from Burkina Faso, 2007. 57, e42-e46. Zoonoses and Public Health, December 2010 doi:10.1111/j.1863-2378.2009.01291.x
  • Mutinelli, F. (2010) Rabies and feral cat colonies in Italy. Vet Rec. Apr 24; 166(17):537-8. doi: 10.1136/vr.c2162.
  • De Benedictis, P., Mutinelli, F., Veggiato, C., Capua, I., Squecco, G., Coassin, R., & Ferri, G. (2009). Rabies in a vaccinated dog in Italy. 165, 216. The Veterinary Record, 15 August http://dx.doi.org/10.1136/vr.165.7.216.
  • Talbi, C., Holmes, E.C., De Benedictis, P., Faye, O., Nakoune, E., Gamatie, D., Diarra, A., Elmamy, B.O., Sow, A., Adjogoua, E.V., Sangare, O., Dundon, W.G., Capua, I., Sall, A.A., & Bourhy, H. (2009). Evolutionary history and dynamics of dog rabies virus in western and central Africa. 90, 783-791. The Journal of General Virology, April 2009 doi:10.1099/vir.0.007765-0
  • De Benedictis, P., Gallo, T., Iob, A., Coassin, R., Squecco, G., Ferri, G., D’Ancona, F., Marangon, S., Capua, I., & Mutinelli, F. (2008). Emergence of fox rabies in North – Eastern Italy. 13, 1-2. Eurosurveillance

Contacts

Director
Paola De Benedictis
E-mail: pdebenedictis@izsvenezie.it
View profile >

Administrative office
Tel.: +39 049 8084371
E-mail: dsbio.izsve@izsvenezie.it

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Istituto Zooprofilattico Sperimentale delle Venezie
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