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Sarah Cleaveland

Institute of Biodiversity, Animal Health and Comparative Medicine

University of Glasgow sarah.cleaveland@glasgow.ac.uk

Canine rabies virus: the disease, the problem and current global recommendations for control and

elimination

OIE-WSAVA conference on rabies and other disease risks from free-roaming dogs, Paris, 5th November 2013

Rabies

A fatal disease in all mammals caused by Lyssavirsues

Rabies virus major cause of problems worldwide

Public health (mortality, morbidity, psychological impacts) Companion animal and livestock health Economic burden Conservation impacts Animal welfare ~100% preventable disease

Large variety of reservoir species

bites and vast majority of human rabies deaths occur in Asia and Africa where dog rabies is

endemic

-reported

Often unable to seek medical attention

Often unable to afford high costs of post-exposure prophylaxis (PEP)

Considerable financial hardship for families raising funds for PEP

Vaccine often not available in rural health centres

A disease of the rural poor

Hampson K et al. (2009) Rabies exposures, post-exposure prophylaxis and deaths in a region of endemic canine rabies: a contact-tracing study. PLoS NTD 2(11): e339.

Delays in PEP related to

distance to economic status

Higher socio-economic status

Lower socio-economic status

Pet animal movements and the re-introduction of canine rabies

No. of dogs legally imported into UK has increased by 65% since 2011

Illegal movements?

Emerging threats

BBC news, 1st November 2013

Rabies introduction can result in very high costs associated with contact tracing and post-exposure prophylaxis

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Rescues and adoptions

Risks of importing rabies highly dependent on compliance with regulations

from other islands

Human-mediated transport - Bali INDONESIA

Incursion in mid 2008 Rapid spread across island >150 human rabies deaths

$2 million/yr in post-exposure vaccinations

~2% of rabid dogs transported

Townsend SE, Sumantra IP, Pudjiatmoko , Bagus GN, et al. (2013) Designing Programs for Eliminati ng Canine Rabies from Islands: Bali, Indonesia as a Case Study. PLoS Negl Trop Dis 7(8): e2372.

Canine rabies and wildlife conservation

Gascoyne et al., JWD, 1993; Kat et al.,Proc. Roy. Soc B., 1995; Sillero-Zubiri et al., JWD 1996; Haydon et al., Conservation Biology, 2002; Randall et al., Emerg. Inf. Dis. 2004; Haydon et al., Nature, 2006

~ 500 individuals Rabies poses most immediate threat to the survival of the species

African wild dog Ethiopian wolf

~5,000 individuals Rabies epidemics have resulted in major population declines and local extinctions

Canine rabies can be controlled and eliminated through mass dog vaccination

or re-emerging with few vaccination success stories

BRAZIL

Perception of too many dogs or too

Perception that dogs are not easily accessible for vaccination

Perception that dog vaccination is too costly to implement within government veterinary services Perception that infection in wildlife would prevent successful dog rabies control/elimination

Some reasons why rabies not yet tackled effectively in Africa

Lembo et al. 2010. PLoS Neglected Tropical Diseases 4: e626.

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Phylogenetic analyses:

A single variant of canine rabies

No sustained chains of wildlife infection

Transmission dominated by dog-to-

dog infection

Metapopulation models:

Spread from external dog

populations not from national park

Intervention studies

Can rabies cycle in wildlife independently of dogs?

Is dog rabies control feasible and cost-effective?

Central Point Vaccination

Engagement of school children is

critical

Coverage high irrespective of socioeconomic status

- People make great efforts to bring their dogs for

vaccination

Vast majority of dogs are owned and accessible for vaccination

Chad - 1%, 8% and 11% of dogs were unowned in three study Kayali et al. 2003)

Zimbabwe All dogs in communal lands were owned (Butler and Bingham, 2000)

Tanzania

< 1% of dogs were unowned in an urban site using mark-recapture observations (Gsell et al. 2013)

No evidence for unowned dogs in any of the communities around the Serengeti (Kaare et al., 2009)

The proportion of unowned dogs is unlikely to be high enough to prevent target vaccination thresholds to be reached

R0 for rabies is VERY low ~1.1-1.3

On average each rabid dog infects 1.2 others

Low value of R0 suggests that elimination should be feasible

Hampson et al. (2009). Transmission dynamics and prospects for elimination of canine rabies. PLoS Biol 7: e53.

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Serengeti:1-10 dogs/km2

60 150 240 330 420 510 600 days

R0=1.2

Bali, Indonesia High density populations

>200 dogs/km2

R0=1.2

Java, 1985 Israel, 1948

R0=1-2 R0=1-2

Mexico, 1987

New York, 1944

Memphis, 1947

R0=1-2

R0=1-2

R0=1-2

Consistently low value of R0 suggests that elimination of canine rabies

through vaccination of 70% dogs is feasible in most settings

Dog population density reduction not very effective for rabies control

Hampson et al. (2009) PLoS Biology Morters et al. (2012) J. Animal Ecology

The problem for rabies control is generally .but

There is demand among dog owners for sterilisation Aggression and nuisance behaviour is problematic and can be a greater concern than rabies in some communities

Improving primary health care important for animal welfare, enhancing life expectancy and reducing demand for puppies Important opportunity for engagement with private practitioners

Rabies control can be achieved quickly

Several studies indicate significant declines in rabies can be seen after two campaigns (Schneider et al., 2007)

Cleaveland et al., (2003) Vaccine, 21: 1965-1973

Agropastoral communities in

Tanzania

Vaccinated villages

Unvaccinated villages

Can result in marked decline in demand

for costly PEP

Protects vulnerable communities unable to access life-saving

PEP promptly

Fitzpatrick M. et al. (in press) Cost-effectiveness of canine vaccination to prevent human rabies in rural Tanzania Annals of Internal Medicine

Total cost

Dog vaccination

Human PEP

Human PEP with no dog vaccination

Dog vaccination highly cost-effective

70% coverage optimal scenario at

-levels of investment

Coverage high in adult and juvenile dogs, but lowest in puppies

- Good response to vaccination regardless of body condition or clinical status (McNabb, 2008)

- Young pups all responded with high titres

Vaccination of puppies

0

10

20

30

40

50

60

70

80

90

100

0 - 0.5 0.5 - 1.0 1.0 - 2.0 2.0 - 3.0 3.0 - 4.0 4.0 - 5.0 5.0 - 6.0

Post-vaccination titre (IU/ml)

<3 mths 3- 6 mths 7-12 mths > 1 yr

At what age should pups be vaccinated?

In mass vaccination campaigns for control of rabies in endemic areas of Africa and Asia, vaccination of pups is important for herd immunity

0

10

20

30

40

50

60

Dog young Dog difficultto handle

Negligence Arrived late Owner away Otherreasons

Not aware ofvaccination

Reason given

However, movement of pups associated with re-introduction of rabies into rabies-free areas

Importation and movement of pups should be discouraged

Dogs must be vaccinated in line with vaccine marketing authorization of importing company

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No outbreaks where vaccination coverage > 70%

Dog rabies can be controlled when achieving a vaccination coverage of ~ 70% during

campaigns

Population immunity remains sufficiently high in interval between campaigns

0

5

10

15

20

25

30

35

No. positive

No. tested

Dog vaccination has resulted in elimination of rabies from some parts

of the ecosystem

Bites from suspected rabid dogs

All dog bites reported to clinics

Although case detection likely to be very low, no canine rabies cases in

Serengeti National Park 2000-2012

Ngorongoro District

Recovery of African wild dog population

sync random rotate source furthest

0

0.5

1

1.5

2

2.5

3

3.5

4

The order and speed of campaigns has little effect on the time it takes for rabies elimination

to occur

Random

1 month campaign

6 month campaigns

Townsend SE, Sumantra IP, Pudjiatmoko , Bagus GN, et al. (2013) Designing Programs for Eliminati ng Canine Rabies from Islands: Bali, Indonesia as a Case Study. PLoS Negl Trop Dis 7(8): e2372.

Simulation models of rabies in Bali, Indonesia

Reached all villages 100% success

3 villages missing 99% success

3 clustered villages missing: <90% success

Clusters of unvaccinated villages and patchy coverage jeopardise rabies control and elimination

Time to elimination depends on completeness of vaccination coverage and rate of re-

introductions

Low vaccination coverage in just 6 out of 75 villages led to resurgence of cases

Frequent introductions from outside vaccinated

area

Serengeti District

Afya Serengeti Project WSAVA dog collar-wrist band study

To determine vaccination coverage in free-roaming dog populations To determine impact on vaccination turn-out To assess duration of collar survival To determine % ownerless dogs

Supported by MSD Animal Health

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Collars and wristbands have increased turnout in all districts

Preliminary results

Estimates of coverage from observations of free-roaming dogs higher than figures from household census

=> Ownerless dogs are not a problem

Probability of detection (%)

1 3 5 7 9

50%

75%

90%

95%

100%

2.5 years without cases (6 months for control + 2 years for elimination) should be sufficient to declare successful elimination of

rabies, even in areas where surveillance is poor (probability of detection <10%)

How long does it take before an area can be declared rabies-free?

Townsend et al. (2013) Surveillance guidelines for disease elimination: a case study of canine rabies. Comparative Immunology, Microbiology and Infectious Diseases 36(3):249-61

Rabies Elimination Demonstration

Projects WHO/Gates Foundation projects in Tanzania,

South Africa and Philippines GARC/UBS Philippines, Indonesia, Chad

Development of regional strategies with

target dates for elimination Latin America 2015 SE Asia - 2020 Africa - 2030?

Building partnerships, building

confidence, breaking down barriers

Working towards the global elimination of canine rabies

www.worldrabiesday.org

Rabies Blueprint

Online tool to support the planning and implementation of rabies control and elimination programmes

www.rabiesblueprint.com

Global Rabies Elimination

would be a blessing for humanity Can we fulfill Global elimination of canine is feasible

Concerted efforts are needed and vigilance is still required

Inoculation of Joseph Meister

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Funding Support Wellcome Trust Medical Research Council, UK Bill and Melinda Gates Foundation World Health Organization NSF Ecology of Infectious Diseases Program UBS Optimus Foundation Leverhulme TrustDepartment for International Development Tusk Trust MSD Animal Health Lincoln Park Zoo Washington State University World Society for the Protection of Animals

Katie Hampson Magai Kaare Dan Haydon Tiziana Lembo

Rabies research team University of Glasgow

Hawthorne Beyer

Sunny Townsend Zac Mtema Sambo Maganga

Acknowledgements University of Glasgow Tiziana Lembo, Katie Hampson, Sunny Townsend, Dan Haydon, Hawthorne Beyer, Zac Mtema, Kirstyn Brunker

University of Pretoria Darryn Knobel

Sokoine University of Agriculture Rudovick Kazwala, Gurdeep Jaswant, Khadija Said

Ministry of Livestock and Fisheries Development, Tanzania Johnson Mollel, District Veterinary Officers

Ifakara Health Institute Lwitiko Sikana, Joel Chagalucha, Maganga Sambo, Kennedy Lushasi

Serengeti Health Initiative Felix Lankester, Imam Mzimbiri, Anna Czupryna, Machunde Bigambo, Kaneja Ibrahim Mangaru, Paulo Charles, Israel Silaa

Animal Health and Veterinary Laboratories Agency, UK Tony Fooks, Dan Horton, Denise Marston Centers for Disease Control and Prevention, USA Charles Rupprecht, Lilliana Orciari, Mike Niezgoda

WHO/Bill and Melinda Gates Project, Tanzania Francois Meslin, Rufaro Chatora, Matthew Maziku, Pelagia Muchuruza, Anastasia Pantelias

ANSES, Nancy, France Jacques Barrat University of Cambridge Michelle Morters, James Wood

Ministry of Health and Social Welfare, Geofrey Mchau, Mohammed Mohammed

Tanzania Veterinary Laboratory Agency Chanasa Ngeleja, Mmeta Yongolo

Serengeti rabies surveillance project Matthias Magoto, Cleophas Simon, Zilpah Kaare

Tanzania Wildlife Research Institute Julius Keyyu, Ernest Eblate, Robert Fyumagwa

Messerli Wildlife Veterinary Project Richard Hoare

Tanzania National Parks Titus Mlengeya

Thank You!

For more information

Global Alliance for Rabies Control

www.globalrabiescontrol.org

World Rabies Day Campaign

www.worldrabiesday.org

Rabies blueprint

www.rabiesblueprint.com