1. What have we achieved since Kiev?: Looking forward Deborah J Briggs, PhD College of Veterinary Medicine Kansas State University

2. 1.Epidemiology 2.Rabies diagnosis 3.Animal rabies control 4.Human rabies prevention 5.Vaccinology and immunology 6.Bat rabies

3. Epidemiology Surveillance – increased sample submission, variant identification in Europe; becomes sporadic or non- existent further EastSurveillance – increased sample submission, variant identification in Europe; becomes sporadic or non- existent further East Increasing data on submissions, negative and positiveIncreasing data on submissions, negative and positive Rabies in Europe Bulletin – increased reporting and support by most European countriesRabies in Europe Bulletin – increased reporting and support by most European countries Fox rabies disappeared in W EuropeFox rabies disappeared in W Europe Epidemiological data becomes sporadic or non- existent farther eastEpidemiological data becomes sporadic or non- existent farther east Threat of re-emergence of rabies by raccoon dogThreat of re-emergence of rabies by raccoon dog

4. Rabies Diagnosis Increasing number of Rabies Reference LaboratoriesIncreasing number of Rabies Reference Laboratories Collaboration and cooperation in EU rabies laboratories – EU very active in support of rabies diagnosesCollaboration and cooperation in EU rabies laboratories – EU very active in support of rabies diagnoses Exchange of samples – WHO/OIE CCsExchange of samples – WHO/OIE CCs Research begun into geographical host species and chronology in EuropeResearch begun into geographical host species and chronology in Europe Need to expand diagnostic capabilities into rabies endemic zones farther eastNeed to expand diagnostic capabilities into rabies endemic zones farther east

5. Animal Rabies Control Eastern Europe – dramatic decrease in rabiesEastern Europe – dramatic decrease in rabies ORV – Eastern Europe and sporadically in AsiaORV – Eastern Europe and sporadically in Asia EU funding opportunities for control programsEU funding opportunities for control programs Minimum financial cost for Rabies control in Europe: 10.04 – 16.84 mio Euros annually – Reduce? Stop?Minimum financial cost for Rabies control in Europe: 10.04 – 16.84 mio Euros annually – Reduce? Stop? Strategy for vaccinating raccoon dogsStrategy for vaccinating raccoon dogs New models – 60% herd immunity could be a useful target in rabies control and save 1/3 of applied resources – opportunities to design a new strategyNew models – 60% herd immunity could be a useful target in rabies control and save 1/3 of applied resources – opportunities to design a new strategy

6. Human rabies and prevention Recent human rabies survival in the US – Why?Recent human rabies survival in the US – Why? NTV replaced in IndiaNTV replaced in India Long lasting memory cells after CCVLong lasting memory cells after CCV Increase usage of low dose intradermal regimens where cost of PEP is prohibitiveIncrease usage of low dose intradermal regimens where cost of PEP is prohibitive Can PreP regimen be reduced?Can PreP regimen be reduced?

7. Vaccinology and Immunology Transfer of vaccine production technologyTransfer of vaccine production technology ELISA for serological testing for animal exportELISA for serological testing for animal export New ORVs under developmentNew ORVs under development Less expensive ORVLess expensive ORV

8. Bat Rabies Widespread surveillance through Europe – increasing attention to bats across Eurasia, AfricaWidespread surveillance through Europe – increasing attention to bats across Eurasia, Africa Establishment of data base for bat viruses – ability to determine bat species through DNA analysesEstablishment of data base for bat viruses – ability to determine bat species through DNA analyses Need protocol standards to compare resultsNeed protocol standards to compare results Spillover into other wildlife speciesSpillover into other wildlife species Need to know species of both positive and negative submitted samples – habitat rangeNeed to know species of both positive and negative submitted samples – habitat range Need for increased surveillance, analyses of genetic diversity & data documentation, pathogenesis, sharing samplesNeed for increased surveillance, analyses of genetic diversity & data documentation, pathogenesis, sharing samples

9. MED VET NET WP05 EBLV Database

12. Changing focus –Changing focus – elimination of rabieselimination of rabies –Broader vision –Cooperation and collaboration –Development of new strategy – bigger picture Expanding region – Asia, AfricaExpanding region – Asia, Africa Rabies is higher on the list of important diseases across the world – more press coverageRabies is higher on the list of important diseases across the world – more press coverage

13. Looking toward our future: Problems or Opportunities? 1.Low priority 2.No major funding 3.Lack of education awareness on all levels 4.Passive immune products – limited availability 5.Treatment in human cases – is it possible?

14. Opportunities Are we willing to take them?

15. Working together for success A house divided cannot standA house divided cannot stand Photo: S Scholand Photo: BJ Mahendra

16. Working together for success Agriculture and Health Ministries must work togetherAgriculture and Health Ministries must work together International, Regional, National, Local levelsInternational, Regional, National, Local levels One medicine approach

17. Vaccinating dogs in Mexico

18. Thailand, years 1995-2004 PEP Source : Bureau of General Communicable Diseases, Department of Disease Control, Ministry of Public Health. RIG RIG 6 to 11 % of PEP

19. Opportunities Can we find money to fund projects?

20. Funding strategies 1.What do we want to fund? 2.Who has that much money that might be willing? 3.How can we achieve funding? Pilot project to eliminate canine rabies from a specific region GATES Organized commitment – together

21. Opportunities Can we find a treatment for human rabies?

22. Human rabies treatment Survival of Wisconsin case – raised many questions: Can human rabies be treated? Need for animal models to validate/extend current observations on fundamental pathogenesis:Need for animal models to validate/extend current observations on fundamental pathogenesis: 1. BH4 deficiencies with associated neurotransmitter deficiencies: now in 3/3 patients - confirm, timing/importance (whether early/primary/ causal of disease or late/secondary), fixed vs wildtype? 2. Vasospasm: confirm, stick in a flow probe, fixed vs wildtype?1. BH4 deficiencies with associated neurotransmitter deficiencies: now in 3/3 patients - confirm, timing/importance (whether early/primary/ causal of disease or late/secondary), fixed vs wildtype? 2. Vasospasm: confirm, stick in a flow probe, fixed vs wildtype?

23. Human rabies treatment Need anti-virals that work: no effect of ketamine/amantadine/ribavirin on salivary viral load until serum neutralizing antibodies are presentNeed anti-virals that work: no effect of ketamine/amantadine/ribavirin on salivary viral load until serum neutralizing antibodies are present Given absence of antivirals, how can we accelerate immunity, safely? Are vaccines safe or not in active disease? Are newer attenuated (double G) constructs different or safer (fixed vs new wildtype/attenuated)?Given absence of antivirals, how can we accelerate immunity, safely? Are vaccines safe or not in active disease? Are newer attenuated (double G) constructs different or safer (fixed vs new wildtype/attenuated)?

24. Opportunities Can we find a solution for limited availability of passive immune products?

25. PEP often delayed; medical education poor in many regionsPEP often delayed; medical education poor in many regions Rabies immunoglobulin is given to less than 3% of patients with severe bites in Asia and AfricaRabies immunoglobulin is given to less than 3% of patients with severe bites in Asia and Africa

26. Passive immunity – product replacement Availability extremely limitedAvailability extremely limited Quality and effectivenessQuality and effectiveness –Pepsin digested heat treated products have lower half life –Testing in vivo not always conducted Mabs for passive immunity in PEP currently undergoing clinical trialsMabs for passive immunity in PEP currently undergoing clinical trials

27. Passive immunity – product replacement de Kruif et al. Annu. Rev. Med. 2007, 58:359-68

28. Opportunities How can we put rabies on the radar screen of the world?

29. WORLD RABIES DAY September 8, 2007 Together we can make rabies history

30. World Rabies Day Facts WHAT: A day of recognition for the ongoing tragedy of rabiesWHAT: A day of recognition for the ongoing tragedy of rabies WHO: OIE (World Animal Health Association), ARC (Alliance for Rabies Control)WHO: OIE (World Animal Health Association), ARC (Alliance for Rabies Control) WHERE: Numerous places throughout the worldWHERE: Numerous places throughout the world WHY: To increase global awareness of rabiesWHY: To increase global awareness of rabies WHEN: September 8, 2007 and annually thereafterWHEN: September 8, 2007 and annually thereafter

31. Partners Support from OIESupport from OIE Pasteur InstitutePasteur Institute Canadian Food Inspection Agency (CFIA)Canadian Food Inspection Agency (CFIA) American Veterinary Medical Association (AVMA)American Veterinary Medical Association (AVMA) American Animal Hospital Association (AAHA)American Animal Hospital Association (AAHA) World Society for the Protection of Animals (WSPA)World Society for the Protection of Animals (WSPA) Commonwealth Veterinary AssociationCommonwealth Veterinary Association Association for the Control of Rabies in India (APCRI)Association for the Control of Rabies in India (APCRI) Rabies in Asia Conference Foundation (RIACON) in IndiaRabies in Asia Conference Foundation (RIACON) in India

32. Sponsors/Partners MerialMerial IntervetIntervet SanofiSanofi NovartisNovartis Berna Biotech/CrucellBerna Biotech/Crucell PfizerPfizer VirbacVirbac

33. WRD - Objectives To improve global awareness of rabies and promote prevention at the local and community levelTo improve global awareness of rabies and promote prevention at the local and community level To mobilize resources for local projects - coordinate global veterinary and medical resources to work together to use one medicine approach to fight rabiesTo mobilize resources for local projects - coordinate global veterinary and medical resources to work together to use one medicine approach to fight rabies To produce and support education initiatives concerning rabies prevention including responsible pet ownershipTo produce and support education initiatives concerning rabies prevention including responsible pet ownership

34. World Rabies Day Involve 55,000 participants around the world - One for every death that need not have occurred

35. World Rabies Day - Opportunities To increase educational awareness and save human livesTo increase educational awareness and save human lives To work together toward elimination of canine rabies – press, veterinarians, medical professionals, governments, international organizationsTo work together toward elimination of canine rabies – press, veterinarians, medical professionals, governments, international organizations To develop and implement national and regional rabies prevention strategiesTo develop and implement national and regional rabies prevention strategies