Controlling dog-mediated rabies in dog demography and vaccination efficacy

V. Chevalier, L. Sowath, L. Pitou, S. Sorn, T. Sothyra, H. Davun, M. Wasnievski, V. Duong, J. Baron, J. Lindhal, P. Dussart, D. Fontenille

Rabies in Cambodia • Population: around 16 Millions – 80% in rural area

 One of the more affected country in the world by Rabies: 800 estimated human deaths/year (Ly, 2009)

 transmitted to humans by dog bites  100% fatal when clinical signs appear  Massive dog vaccination is an efficient way to protect humans

2 Rationale

• To be efficient, dog vaccination needs to – Be adapted to dog population characteristics – Induce long lasting immunity – Be cost effective – Acceptable for owners – Feasible

=> Objectives

– Basic knowledge on dog populations – Dog population dynamics – Dog-human relationships – Bite incidence – Massive vaccination feasability – Vaccination coverage dynamic at Individual and population levels Comprehensive door-to-door dog follow-up

• 2017-2019 • Individually identified • Age, Sex • « Use » • Origin • Body Score Condition • Confinement • Pregnant status • Puppies management • Consumption practices • Bite events (past year) • Vaccination against rabies • Post vaccination Serological follow up (FAVN test) Dog/human ratios

Battambang province 3010 dogs => ~ 5 Millions Dog/human ratio dogs in 1:3 Cambodia, [1:2 - 1:6] heterogenous distribution Kandal province 2205 dogs Dog/human ratio 1:4 [1:3 - 1:11 ] Large differences between villages Dog population survival Kaplan Meier estimate

Survival probabilities

12 months : 62% (IC50: 0.60- 0.64) => µ= 47%!

24 months: 52% (IC50 :0.50-0.55) => µ= 33% Log-rank test

36 months :46% (IC50: 0.43- 0.48) => µ= 26%

Dog population survival

60%

Village F

Village A 30%

Village A : 30% at 48 months To be considered for Village F : 60% at 48 months vaccination plans Population dynamic and vaccination coverage

• vaccination coverage T0 • Stable population • Yearly constant vaccination rate without dog marking

T(t+1) = exp(- µ)*(1-(1-Tx(t))*(1-v1)) + (1-exp(- µ))*v1

survival rate at year t+1 of dogs present at year t Renewal rate

(1-(1-Tx(0))*(1-v1)) is the probability of being vaccinated , either in year 0 or year 1, or 2 or n….

Population dynamic and vaccination coverage OIE recommends a 70% vaccination coverage A high renewal rate implies a high vaccination frequency !

• Total population : µ=0,18 • Village A : µ=0,31 • Yearly vaccination of 30% (1.5M) or 50% (2.5M) of dogs

Mortality rate and Spatial heterogeneity crucial => more information on dog movements, mortality an related factors Dog ownership

Number of dogs/family/village • Predictors of the number of dogs per family to focus information/vaccination campaigns

• 1 to 14 dogs per family

• Negative binomial regression model

– Head of family = male (p<0.001)

– number of children <15years (p<0.01)

– more dogs/family in rural villages compared to peri-urban (p< 0.001) Bite incidence and risk factors

3 bite events /100pers/yr => 500 000 bites events/yr in Cambodia 70% caused by dogs, others by cats

Seasonality Negative binomial regression results

incidence rate ratios Estimate Pr(>|z|) estimate Intercept 0.02671 0.900006 1.02 Number of children <15 0.16281 0.000167 *** 1.18 Number of dogs 0.13033 1.1e-05 *** 1.14 BOENG PREY 0.44348 0.026459 * 0.64 0.58168 0.030139 * 0.56 KAMPANG LECH 0.25840 0.401966 0.77 PREAH SRE 0.19582 0.427371 0.82 RUM CHEY 0.01160 0.959316 1.01 KEUT 0.07010 0.738592 1.07 SNOENG KEUT 0.46710 0.086324 . 0.63 Cold season Hot season 0.15308 0.511649 0.85 Rainy season 2.55901 < 2e-16 *** 0.08

FAVN test for Rabies virus

• Fluorescent Antibody Virus Neutralization (FAVN) test – Quantification of rabies-neutralizing antibody – Measure antibody response to rabies vaccination • Purpose – Individual animal freedom from infection prior movement – Immune status in individual animal or populations post- vaccination – Contribute to eradication policies . The minimum measurable neutralizing antibody titer considered to represent a reasonable level of seroconversion is 0.5 IU/ml – In dogs and cats

. Set-up of FAVN test at IPC in 2019, and 1 one week regional training – with support from ANSES Nancy, Laboratory for Rabies and Wildlife – NIHE, Nuol

A new PhD student!

• Co-supervised by IPC, CIRAD and Davis University

• Updated burden estimation of Rabies in Cambodia using Bayesian methods

• Agent Based, Spatially Explicit Simulation Modelling of Rabies – Model dog-human interaction at the village level, including dog bite-injuries as well as rabies transmission from dogs to humans – Evaluate the impact of long-distance travel in terms of rabies spread between villages and identify high-risk transmission pathways.

– Calculate R0 values both at the village and district level

• Use the model to assess efficiency of different control strategies Thank you for attention !

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