1) Rabies is a fatal viral disease transmitted primarily through animal bites. It remains a global public health problem, causing tens of thousands of deaths annually, especially in Africa and Asia. 2) Effective prevention and control of rabies relies on a multi-sectoral "One Health" approach involving veterinary, public health and wildlife agencies. Key strategies include dog vaccination programs, post-exposure prophylaxis for bite victims, and oral rabies vaccination of wildlife in some regions. 3) While still present, rabies transmission has been eliminated from dog populations in the United States and parts of Latin America through well-coordinated vaccination and public education efforts. However, rabies persists in wildlife reservoirs in many areas

1. 1
One Health in the Prevention and Control of
Rabies
Darin S. Carroll PhD
Chief, Poxvirus and Rabies Branch
Division of High Consequence Pathogens and Pathology
US Centers for Disease Control and Prevention

2. 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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3. 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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4. 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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5. 5
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

6. 66
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
.

7. Rabies Ecology
RABIES RESERVOIRS
Enzootic rabies
SUSCEPTIBLE SPECIES
Dead ends
Cows
Goats
and
Sheep
Humans and
horses
PigsBeavers and
woodchucks
Big
brown
bat
Gray fox
Stripped
skunk
MongooseSpotted
skunk
Raccoon
dog
Vampire bat
Silver
hair bat
Red batHoary bat Free tail bat
Raccoon Coyote Arctic foxDog

8. 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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9. 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

10. 1010
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

11. 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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12. Epidemiological Trends of
Human and Canine Rabies Cases (N=7,228)
Latin America, 1970–2009
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0
50
100
150
200
250
300
350
400
1970 1973 1976 1979 1982 1985 1988 1991 1994 1997 2000 2003 2006 2009
0
5000
10000
15000
20000
25000
30000
Human cases
Rabid dogs
1984: >300 human cases
2009: 19 human cases; 95% reduction of human and dog cases
Numberofrabiescases
PAHO Rabies Information System, SIRVERA (www.panaftosa.org.br). Updated December 2010. Accessed Jan 18, 2011

13. Species Interface Event Consequence
*African wild dog Spillover of canine variant into
African wild dog
Threatens 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 control
Profound conservation impacts

14. 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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15.  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 Rabies
Integration of Tools

16. Rabies: Diagnostics
Rupprecht CE, et al. Lancet Infect Dis. 2002;2:327-343
CNS, Central nervous system
DFA, 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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17. 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

18. World Rabies Day
September 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