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 16 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) 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 40 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). Rabies control is a top priority for the EU, which has called for the elimination of wildlife rabies in EU countries by 2020.
Intriguingly, bats are the sole reservoir of 15 known lyssaviruses worldwide, and hence are the true reservoirs. In contasrt to the classical rabies virus (RABV) bat –associated lyssaviruses have a narrower geographic and host range distribution. Even for RABV bats are a main reservoir, however only in in the Americas). For two further lyssaviruses it is presumed that bats are the reservoirs too. European bats can also develop rabies disease and die. Most strongly affected are Serotine bats, which have been shown to harbor European bat lyssavirus 1 (EBLV-1). Pond bats and Daubenton’s bats are the reservoirs for EBLV-2, while the Natterer’s bat is the reservoir for Bokeloh bat lyssavirus (BBLV). The West Caucasian bat lyssavirus (WCBV) and the Lleida bat lyssavirus (LLEBV) have been detected in sub species of the Schreiber’s bat (Miniopterus schreibersii) in West Caucasia, Spain and France, respectively. Bats of this species are seen only rarely as migratory animals in Germany.
The terms of reference (ToR) as National Reference Laboratory for Rabies [national legislation on rabies control (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)]:
- 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
The FLI has been designated a WHO Collaborating Centre for Rabies Surveillance and Research and an OIE Reference Laboratory for Rabies in 1975 and 1992, respectively. Terms of Reference (ToR) are defined with each re-designation period:
ToR as WHO Collaborating Centre for Rabies Surveillance and Research and OIE Reference Laboratory for Rabies:
- 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), direct rabies immunohistochemical test (DRIT) & immunochromatographic test (later flow device)
- Virus detection in cell culture (RTCIT - virus isolation)
- Lyssavirus genome detection by conventional and real-time RT-PCR assays
- Genetic characterization of lyssavirus strains by next generation and classical sequencing
- Biological characterization of lyssavirus strains in mouse model
- Antibody detection by neutralization test, ELISA, Cell-ELISA and immunoblotting
- Pathogenicity studies with novel lyssaviruses
- Passive surveillance on the occurrence of lyssavirus infections
- Characterization of lyssavirus isolates from Europe and elsewhere
- Collection and analysis of rabies surveillance data from Europe
- Immunogenicity and efficacy of novel oral rabies vaccines
- Oral vaccination of wildlife and dogs
- Technical advice for the control of dog-mediated rabies in Namibia
- Kudu rabies