What have we achieved What have we achieved since Kiev?: Looking since Kiev?: Looking

forwardforward

Deborah J Briggs, PhDDeborah J Briggs, PhD

College of Veterinary MedicineCollege of Veterinary Medicine

Kansas State UniversityKansas State University

1.1. EpidemiologyEpidemiology2.2. Rabies diagnosisRabies diagnosis3.3. Animal rabies controlAnimal rabies control4.4. Human rabies preventionHuman rabies prevention5.5. Vaccinology and immunologyVaccinology and immunology6.6. Bat rabiesBat rabies

EpidemiologyEpidemiology• Surveillance – increased sample submission, Surveillance – increased sample submission,

variant identification in Europe; becomes variant identification in Europe; becomes sporadic or non-existent further Eastsporadic or non-existent further East

• Increasing data on submissions, negative and Increasing data on submissions, negative and positivepositive

• Rabies in Europe Bulletin – increased reporting Rabies in Europe Bulletin – increased reporting and support by most European countriesand support by most European countries

• Fox rabies disappeared in W Europe Fox rabies disappeared in W Europe • Epidemiological data becomes sporadic or non-Epidemiological data becomes sporadic or non-

existent farther eastexistent farther east• Threat of re-emergence of rabies by raccoon Threat of re-emergence of rabies by raccoon

dog dog

Rabies DiagnosisRabies Diagnosis• Increasing number of Rabies Increasing number of Rabies

Reference LaboratoriesReference Laboratories• Collaboration and cooperation in EU Collaboration and cooperation in EU

rabies laboratories – EU very active in rabies laboratories – EU very active in support of rabies diagnosessupport of rabies diagnoses

• Exchange of samples – WHO/OIE CCsExchange of samples – WHO/OIE CCs• Research begun into geographical Research begun into geographical

host species and chronology in Europe host species and chronology in Europe • Need to expand diagnostic capabilities Need to expand diagnostic capabilities

into rabies endemic zones farther eastinto rabies endemic zones farther east

Animal Rabies ControlAnimal Rabies Control• Eastern Europe – dramatic decrease in rabiesEastern Europe – dramatic decrease in rabies• ORV – Eastern Europe and sporadically in Asia ORV – Eastern Europe and sporadically in Asia • EU funding opportunities for control programsEU funding opportunities for control programs• Minimum financial cost for Rabies control in Minimum financial cost for Rabies control in

Europe: 10.04 – 16.84 mio Euros annually – Europe: 10.04 – 16.84 mio Euros annually – Reduce? Stop?Reduce? Stop?

• Strategy for vaccinating raccoon dogsStrategy for vaccinating raccoon dogs• New models – 60% herd immunity could be a New models – 60% herd immunity could be a

useful target in rabies control and save 1/3 of useful target in rabies control and save 1/3 of applied resources – opportunities to design a applied resources – opportunities to design a new strategynew strategy

Human rabies and Human rabies and preventionprevention

•Recent human rabies survival in the Recent human rabies survival in the US – Why?US – Why?

•NTV replaced in India NTV replaced in India •Long lasting memory cells after CCV Long lasting memory cells after CCV • Increase usage of low dose Increase usage of low dose

intradermal regimens where cost of intradermal regimens where cost of PEP is prohibitivePEP is prohibitive

•Can PreP regimen be reduced?Can PreP regimen be reduced?

Vaccinology and Vaccinology and ImmunologyImmunology

• Transfer of vaccine production Transfer of vaccine production technologytechnology

• ELISA for serological testing for ELISA for serological testing for animal exportanimal export

• New ORVs under developmentNew ORVs under development• Less expensive ORVLess expensive ORV

Bat RabiesBat Rabies• Widespread surveillance through Europe – Widespread surveillance through Europe –

increasing attention to bats across Eurasia, increasing attention to bats across Eurasia, AfricaAfrica

• Establishment of data base for bat viruses – Establishment of data base for bat viruses – ability to determine bat species through DNA ability to determine bat species through DNA analysesanalyses

• 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 Need to know species of both positive and

negative submitted samples – habitat rangenegative submitted samples – habitat range• Need for increased surveillance, analyses of Need for increased surveillance, analyses of

genetic diversity & data documentation, genetic diversity & data documentation, pathogenesis, sharing samplespathogenesis, sharing samples

MED VET NET MED VET NET WP05 EBLV WP05 EBLV

DatabaseDatabase

• Changing focus – Changing focus – • ‘‘elimination’ of rabieselimination’ of rabies

– Broader visionBroader vision– Cooperation and collaborationCooperation and collaboration– Development of new strategy – bigger Development of new strategy – bigger

picture picture • Expanding region – Asia, AfricaExpanding region – Asia, Africa• Rabies is higher on the list of Rabies is higher on the list of

important diseases across the world – important diseases across the world – more press coveragemore press coverage

Looking toward our future:Looking toward our future:Problems or Opportunities?Problems or Opportunities?

1.1.Low priority Low priority

2.2.No major fundingNo major funding

3.3.Lack of education awareness on all Lack of education awareness on all levelslevels

4.4.Passive immune products – limited Passive immune products – limited availabilityavailability

5.5.Treatment in human cases – is it Treatment in human cases – is it possible?possible?

OpportunitOpportunitiesies

Are we willing to Are we willing to take them?take them?

Working together for Working together for successsuccess

• ““A house divided cannot stand”A house divided cannot stand”

Photo: S Scholand

Photo: BJ Mahendra

Working together for Working together for successsuccess

• Agriculture and Health Ministries must work Agriculture and Health Ministries must work togethertogether

• International, Regional, National, Local levelsInternational, Regional, National, Local levels

““One medicine approach” One medicine approach”

7.1 7.5

9.1 9.3 9.710.6 10.9 11.1

12.613.3 13.7

14.915.9 16.2

14.5

29

76105

1600

1382

3049

2106

2253

1387

852

523335 317

244117

0

2

4

6

8

10

12

14

16

18

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

0

500

1000

1500

2000

2500

3000

3500

Vaccinating dogs in Vaccinating dogs in MexicoMexico

Thailand, years 1995-2004Thailand, years 1995-2004

160,443176,118

207,808

234,394 239,698

340,394

401,181

24,1

93

390,408

24,8

63

344,321

22,2

18

351,535

30,6

78

0

50,000

100,000

150,000

200,000

250,000

300,000

350,000

400,000

450,000

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

PEP

Source : Bureau of General Communicable Diseases, Department Source : Bureau of General Communicable Diseases, Department of Disease Control, Ministry of Public Health.of Disease Control, Ministry of Public Health.

RIGRIG

RIG

6 to 11 % of PEP

OpportunitOpportunitiesies

Can we find money to Can we find money to fund projects?fund projects?

Funding strategiesFunding strategies

1.1. What do we want to fund?What do we want to fund?

2.2. Who has that much money that might Who has that much money that might be willing?be willing?

3.3. How can we achieve funding?How can we achieve funding?

Pilot project to eliminate canine rabies from a specific region

GATES

Organized commitment – together

OpportunitOpportunitiesies

Can we find a Can we find a treatment for human treatment for human

rabies?rabies?

Human rabies treatmentHuman rabies treatmentSurvival of Wisconsin case – raised many Survival of Wisconsin case – raised many

questions:questions: Can human rabies be treated? Can human rabies be treated?• Need for animal models to validate/extend Need for animal models to validate/extend

current observations on fundamental current observations on fundamental pathogenesis:pathogenesis:

• 1. BH4 deficiencies with associated 1. BH4 deficiencies with associated neurotransmitter deficiencies: now in 3/3 neurotransmitter deficiencies: now in 3/3 patients - confirm, timing/importance patients - confirm, timing/importance (whether early/primary/ causal of disease or (whether early/primary/ causal of disease or late/secondary), fixed vs wildtype?late/secondary), fixed vs wildtype?

2. Vasospasm: confirm, stick in a flow probe, 2. Vasospasm: confirm, stick in a flow probe, fixed vs wildtype?fixed vs wildtype?

Human rabies treatmentHuman rabies treatment

• Need anti-virals that work: no effect of Need anti-virals that work: no effect of ketamine/amantadine/ribavirin on salivary ketamine/amantadine/ribavirin on salivary viral load until serum neutralizing antibodies viral load until serum neutralizing antibodies are presentare present

• Given absence of antivirals, how can we Given absence of antivirals, how can we accelerate immunity, safely?accelerate immunity, safely?     Are vaccines safe or not in active disease?     Are vaccines safe or not in active disease?     Are newer attenuated (double G)      Are newer attenuated (double G) constructs different or safer (fixed vs new constructs different or safer (fixed vs new wildtype/attenuated)?wildtype/attenuated)?

OpportunitOpportunitiesiesCan we find a Can we find a

solution for limited solution for limited availability of passive availability of passive

immune products?immune products?

• PEP often delayed; medical education PEP often delayed; medical education poor in many regionspoor in many regions

• Rabies immunoglobulin is given to less Rabies immunoglobulin is given to less than 3% of patients with severe bites in than 3% of patients with severe bites in Asia and AfricaAsia and Africa

Passive immunity – product Passive immunity – product replacementreplacement

• Availability extremely limitedAvailability extremely limited• Quality and effectivenessQuality and effectiveness

– Pepsin digested heat treated products Pepsin digested heat treated products have lower half lifehave lower half life

– Testing in vivo not always conductedTesting in vivo not always conducted

• Mabs for passive immunity in PEP Mabs for passive immunity in PEP currently undergoing clinical trials currently undergoing clinical trials

Passive immunity – product Passive immunity – product replacementreplacement

de Kruif et al. Annu. Rev. Med. 2007, 58:359-68

OpportunitOpportunitiesies

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

WORLD RABIES DAYWORLD RABIES DAYSeptember 8, 2007September 8, 2007

Together we can make rabies history

World Rabies Day FactsWorld Rabies Day Facts

• WHAT:WHAT: A day of recognition for the ongoing A day of recognition for the ongoing tragedy of rabiestragedy of rabies

• WHO:WHO: OIE (World Animal Health Association), OIE (World Animal Health Association), ARC (Alliance for Rabies Control)ARC (Alliance for Rabies Control)

• WHERE: WHERE: Numerous places throughout the Numerous places throughout the worldworld

• WHY: WHY: To increase global awareness of rabiesTo increase global awareness of rabies• WHEN: WHEN: September 8, 2007 and annually September 8, 2007 and annually

thereafterthereafter

PartnersPartners

• Support from OIESupport from OIE• Pasteur Institute Pasteur 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 Association for the Control of Rabies in India

(APCRI)(APCRI)• Rabies in Asia Conference Foundation (RIACON) in Rabies in Asia Conference Foundation (RIACON) in

IndiaIndia

Sponsors/PartnersSponsors/Partners

•MerialMerial• Intervet Intervet •SanofiSanofi•NovartisNovartis•Berna Biotech/CrucellBerna Biotech/Crucell•Pfizer Pfizer •Virbac Virbac

WRD - ObjectivesWRD - Objectives

• To improve global awarenessTo improve global awareness of rabies and of rabies and promote prevention at the local and promote prevention at the local and community levelcommunity level

• To mobilize resources for local projectsTo mobilize resources for local projects - - coordinate global veterinary and medical coordinate global veterinary and medical resources to work together to use one resources to work together to use one medicine approach to fight rabiesmedicine approach to fight rabies

• To produce and support education To produce and support education initiativesinitiatives concerning rabies prevention concerning rabies prevention including responsible pet ownershipincluding responsible pet ownership

World Rabies World Rabies DayDay

Involve 55,000 participants Involve 55,000 participants around the worldaround the world

- One for every death that - One for every death that need not have occurredneed not have occurred

World Rabies Day - World Rabies Day - OpportunitiesOpportunities

• To increase educational awareness and To increase educational awareness and save human livessave human lives

• To work together toward elimination of To work together toward elimination of canine rabies – press, veterinarians, canine rabies – press, veterinarians, medical professionals, governments, medical professionals, governments, international organizationsinternational organizations

• To develop and implement national and To develop and implement national and regional rabies prevention strategiesregional rabies prevention strategies