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One Health in the Prevention and Control of Rabies

Darin S. Carroll PhDChief, Poxvirus and Rabies Branch

Division of High Consequence Pathogens and PathologyUS Centers for Disease Control and Prevention

Etiology

RNA viruses in the family Rhabdoviridae, genus Lyssavirus The type species of the genus is Rabies Virus

All mammals appear susceptible; some groups serve as reservoirs

Kuzmin I, et al. Virus Res. 2010;149:197–210, ICTV, 2012.RNA, Ribonucleic acid

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Rabies: Clinical Stages

Incubation period Range: 6 days to >2 years Average: 4–6 weeks

Prodromal stage Nonspecific signs

Acute neurologic phase Coma Death

Vs. extremely rare reports of experimental treatment and recovery from rabies after the onset of clinical signs

Hemachudha T, et al. Principles Neurol Infect Dis. McGraw-Hill. 2005:151-176

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Rabies: Pathogenesis

Transmission primarily via bite Viruses are highly neurotropic

Enter peripheral nerves Centripetal travel by retrograde flow in

axoplasm of nerves Replicate in CNS Centrifugal flow to innervated organs,

including the primary portal of exit, the salivary glands

Viral excretion in saliva

Dietzschold B, et al. Future Virol. 2008;3:481-90.CNS, Central nervous system

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1 Rabies virus (RABV)

2 Lagos bat (LBV) 1956

3 Mokola (MOKV) 1968

4 Duvenhage (DUVV) 1970

5 European bat lyssavirus type 1 EBLV-1 1992

6 European bat lyssavirus type 2 EBLV-2 1995

7 Australian bat lyssaviruses (ABLV) 1996

8 Aravan 1991

9 Khujand 2001

10 Irkut 2002

11 West Caucasian bat virus (WCBV) 2002

12 Shimoni bat virus (SHBV), 2009

13 Ikoma lyssavirus (IKOV), 2009

13 Bokeloh bat lyssavirus (BBLV), 2010

14 Lleida bat lyssavirus (LLEBV), 2012 tentative status

Lyssavirus Classification

3 lyssavirus clades Some lacking cross reactivity

to commercial biologics

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Etiology and definition

The highest case fatality rate of any known human pathogen (100% lethal but 100% preventable)

One health paradigm for disease control Veterinary, Public Health and Wildlife agencies

Distributed on all continents but Antarctica One of the oldest described infectious diseases,

known for more than 4 thousand years

WHO World Health Organ Tech Rep Ser. 2005;931:1-88

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Rabies Ecology

RABIES RESERVOIRS

Enzootic rabies

SUSCEPTIBLE SPECIES

Dead ends

Cows

Goats and

Sheep

Humans and horses

PigsBeavers and

woodchucks

Big brown batGray fox

Stripped skunk MongooseSpotted skunkRaccoon dog

Vampire batSilver hair bat

Red batHoary bat Free tail bat

Raccoon Coyote Arctic foxDog

Rabies: Global Burden

Human rabies exposures/year: Tens of millions Estimated human rabies deaths/year: >59,000

Africa (rural): 3.6/100,000 India (rural): 2.5 /100,000 Pakistan: 1.2/100,000 China: 0.2/100,000

Most cases occur in Africa and Asia, and in children Reservoirs

Domestic dog: Single most important animal reservoir Wildlife important, especially in Europe and North America

Knobel D, et al. Bull World Health Organ. 2005;83:360-8.

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Why Do People Still Die of Rabies?

Lack of awareness on all levels about Responsible pet ownership – vaccinating pets Need for post-exposure prophylaxis (PEP) Primary wound care

Rabies vaccines are too expensive

Rabies vaccines (PEP) not widely available

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Slide courtesy of Dr Katie Hampson, University of Glasgow

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Dogs and Rabies Transmission

Worldwide >90% of rabies exposures are from dogs

Worldwide >99% of human rabies deaths are via dogs

Rabies control and elimination is possible in dogs

Rabies in the United States

Human rabies: Uncommon 20,000–40,000 exposures/year 1–8 cases/year

Animal rabies 7,000 –10,000 cases/year Dog rabies transmission eliminated Wildlife hosts include raccoons,

skunks, foxes, mongooses (Puerto Rico), and bats

Distributed in every state but Hawaii

Blanton JD, et al. J Am Vet Med Assoc. 2009;235:676-89

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Epidemiological Trends of Human and Canine Rabies Cases (N=7,228)

Latin America, 1970–2009

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50

100

150

200

250

300

350

400

1970 1973 1976 1979 1982 1985 1988 1991 1994 1997 2000 2003 2006 20090

5000

10000

15000

20000

25000

30000

Human cases

Rabid dogs

1984: >300 human cases2009: 19 human cases; 95% reduction of human and dog cases

Num

ber o

f rab

ies

case

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PAHO Rabies Information System, SIRVERA (www.panaftosa.org.br). Updated December 2010. Accessed Jan 18, 2011

Species Interface Event Consequence *African wild dog Spillover of canine variant into

African wild dogThreatens local extirpation

*Ethiopian wolf Spillover of canine variant into Ethiopian wolf

Threatens species extinction

Coyote Spillover of canine variant from Mexico into coyote

Creates a public health emergency in south Texas

Gray fox Spillover of gray fox variant into dog

Confounds success of ORV in gray foxes

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* Endangered species

Dog-Wildlife Interface

Achieving objectives of dog and wild carnivore rabies controlProfound conservation impacts

Rabies: Foundations of Prevention and Control

Vaccination of dogs (70% of the population)

Minimization of human exposures to infected animals

Prompt wound care and prophylaxis with vaccine and rabies immune globulin after exposure

Rupprecht CE, et al. Devel Biol (Basel). 2008;131:95-121

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Education (Avoid bites but report them)

Regulations (vaccination/importation laws)

Quarantine Dog Vaccination Campaigns

Oral Rabies Vaccination (ORV) in wildlife

Spay/neuter/Contraception to control dog populations

Effective and efficient diagnostics

Effective Control of Dog RabiesIntegration of Tools

Rabies: Diagnostics

Rupprecht CE, et al. Lancet Infect Dis. 2002;2:327-343CNS, Central nervous systemDFA, Direct fluorescent antibody

Efficient Laboratory Diagnostics Gold standard: Postmortem demonstration

of viral antigens in CNS by DFA In humans, antemortem detection of virus

or viral amplicons, antibodies, or antigens (sera, CSF, saliva, nuchal biopsy)

Allows for targeting resources to minimize waste

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Lessons Learned

Rabies prevention is possible Need support from multiple sectors Agricultural and Public Health Ministries must

work together Public/private partnerships are critical – pooling of

resources Communication networks are powerful

World Rabies Day First global webinar included >2,000 participants

from 34 countries

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dRIT, direct Rapid Immunochistochemical Test

World Rabies DaySeptember 28

Since September 2007… 135 participating countries 150+ participating schools of public health,

veterinary and medical colleges have hosted one or more ‘rabies-awareness events

~300K Web visitors, 214 countries/territories

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www.worldrabiesday.org