What have we achieved since Kiev Looking

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

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

Epidemiology • Surveillance – increased sample submission, variant identification in Europe; becomes sporadic or nonexistent further East • Increasing data on submissions, negative and positive • Rabies in Europe Bulletin – increased reporting and support by most European countries • Fox rabies disappeared in W Europe • Epidemiological data becomes sporadic or nonexistent farther east • Threat of re-emergence of rabies by raccoon dog

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

Animal Rabies Control • • • Eastern Europe – dramatic decrease in rabies ORV – Eastern Europe and sporadically in Asia EU funding opportunities for control programs Minimum financial cost for Rabies control in Europe: 10. 04 – 16. 84 mio Euros annually – Reduce? Stop? Strategy 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 strategy

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

Vaccinology and Immunology • • Transfer of vaccine production technology ELISA for serological testing for animal export New ORVs under development Less expensive ORV

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

MED VET NET WP 05 EBLV Database

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

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

Opportunities Are we willing to take them?

Working together for success • “A house divided cannot stand” Photo: S Scholand Photo: BJ Mahendra

Working together for success • Agriculture and Health Ministries must work together • International, Regional, National, Local levels “One medicine approach”

Vaccinating dogs in Mexico

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

Opportunities Can we find money to fund projects?

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

Opportunities Can we find a treatment for human rabies?

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: • 1. BH 4 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?

Human rabies treatment • Need 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)?

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

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

Passive immunity – product replacement • Availability extremely limited • Quality 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 trials

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

Opportunities How can we put rabies on the ‘radar screen’ of the world?

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

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

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

Sponsors/Partners • Merial • Intervet • Sanofi • Novartis • Berna Biotech/Crucell • Pfizer • Virbac

WRD - Objectives • To 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 rabies • To produce and support education initiatives concerning rabies prevention including responsible pet ownership

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

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