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Institute of Molecular Virology and Cell Biology (IMVZ)

OIE and National Reference Laboratory for Rabies

WHO Collaborating Centre for Rabies Surveillance and Research 

Rabies, one of the oldest known viral zoonotic diseases, i.e. diseases that are transmissible from animals to humans, occurs worldwide and is an internationally notifiable disease. According to estimations of the WHO still several tens of thousands of humans die from this disease every year, especially in the poorer countries of Africa and Asia. Therefore, it is also considered a neglected zoonosis. 

Rabies is an acute, progressive and incurable viral encephalitis caused by negative strand RNA viruses of the Lyssavirus genus, family Rhabdoviridae of the Mononegavirales order that is transmitted following bites of infected mammals. The recognized etiological agents are classified into 14 recognized and 2 putative Lyssavirus species. Rabies virus (RABV), the causative agent of „classical or terrestrial rabies“, has a worldwide distribution with a variety of mesocarnivores (dog, fox, coyote, raccoon, raccoon dog, mongoose) and bats (in the Americas) as main reservoirs. 

From an epidemiological point of view, classical rabies can be differentiated into a „sylvatic “ and „urban“ cycle. While sylvatic rabies designates rabies transmitted by wildlife carnivores, dogs (Canis canis) are the main reservoir of urban rabies. The reservoir hosts independently maintain the infectious cycle thereby transmitting rabies virus to other animals and humans. In Europe, the red fox (Vulpes vulpes) is responsible for the persistence and spread of the disease. 

In the past 35 years, rabies control in Europe has been as successful as never before. The implementation of oral rabies vaccination (ORV) of foxes using modified live rabies vaccines virtually resulted in the elimination of the disease in Europe and Germany. Like other Western and Central European countries, in 2008 Germany was officially declared rabies-free (freedom from classical rabies). 

Intriguingly, bats are the reservoir of 15 further lyssaviruses worldwide. European bats can also develop rabies disease and die. Most strongly affected are European and North African serotine bats, which have been shown to carry the European bat lyssavirus 1 (EBLV-1). Pond bats and Daubenton’s bats are the reservoir for EBLV-2. Recently, a new lyssavirus, the Bokeloh bat lyssavirus (BBLV), has been detected in a Natterer’s bat in Germany and France. The West Caucasian bat lyssavirus (WCBV) and the Lleida bat lyssavirus (LLEBV) have been detected in west Caucasia and Spain, each in a diseased Schreiber’s bat (Miniopterus schreibersii). In Germany, bats of this species are seen only rarely as migratory animals.

The terms of reference (ToR) as a WHO Collaborating Centre for Rabies Surveillance and Research and an OIE Reference Laboratory for Rabies are defined with the designation by WHO (1975) and the OIE (1992).  The tasks of the national reference laboratory (NRL) for rabies are derived from rabies regulation (TW-VO) of 11 April 2001 (Federal Law Gazette I 2001 p. 598) in association with a decision of the German Ministry of Nutrition and Agriculture dated 08 July 1997. 

The terms of reference (ToR) as a WHO Collaborating Centre for Rabies Surveillance and Research and an OIE Reference Laboratory for Rabies ToR as NRL for Rabies:

  • To undertake consultative work for federal and state veterinary authorities upon request and provide expertise for surveillance and rabies control
  • To conduct and coordinate research on lyssavirus diagnosis, pathogenesis, epidemiology and immunization 
  • To standardize rabies diagnostic techniques & reagents
  • Provision of virus strains and reference sera
  • To conduct batch release of rabies diagnostics 
  • To confirm rabies diagnosis upon request
  • Organization of national inter-laboratory proficiency tests

Terms of Reference as WHO Collaborating Centre for Rabies Surveillance and Research (http://apps.who.int/whocc/Detail.aspx?cc_ref=DEU-52&) and OIE Reference Laboratory for Rabies (http://www.oie.int/our-scientific-expertise/reference-laboratories/introduction/):

  • To conduct and coordinate research on rabies based upon recommendations of the WHO expert committees, scientific groups and other consultative meetings. Areas of research are oral vaccination of wildlife & dogs, epidemiological and laboratory diagnostics of rabies, and epidemiology of rabies in neozoa and European bats. 
  • To collect & analyze rabies surveillance data & to distribute the information to collaborating institutes. To further develop the European database for rabies (www.who-rabies-bulletin.org/) as an interdisciplinary platform and information source of rabies surveillance & research in Europe and as a template for other regions. 
  • To contribute to the Global Health Observatory of the WHO by providing expert knowledge and available rabies surveillance and related data or information 
  • To provide support & expertise for surveillance & control measures of rabies 
  • To provide training in the fields of epidemiology & laboratory diagnostics. 
  • To standardize techniques & reagents & distribute WHO reagents to other laboratories. 
  • To undertake consultative work for WHO & other laboratories upon request.  
  • Antigen detection by immunofluorescence test (IFT)
  • Virus detection in cell culture (RTCIT - virus isolation)
  • Genome detection by conventional and real-time RT-PCR
  • Multiplex real-time RT-PCR for differentiation of field and vaccine virus
  • Multiplex real-time RT-PCR for differentiation of EBLV-1 und -2
  • Virus strain characterization by genome sequencing
  • Antibody detection by neutralization test, ELISA and immunoblotting
  • Panel of 30 reference sera
  • Different rabies virus reference strains
  • Sample panels of 10 anti-nucleocapsid monoclonal antibodies for virus typing
  • Pathogenicity studies with EBLV-1 & -2 virus variants
  • Passive surveillance on the occurrence of EBLV infections of indigenous bats
  • Genotypical characterization of EBLV isolates from Europe
  • Development of Lyssavirus-genotype specific real-time RT-PCRs
  • Collection and analysis of rabies data from Europe
  • Accompanying scientific investigations for the development of rabies vaccines
  • Development of a monoclonal antibody cocktail for human post-exposure prophylaxis
  • Rabies regulation (TW-VO) of 11 April 2001 (Federal Law Gazette I 2001 p. 598)