Phylogenetic and phylodynamic analysis of the diffusion of dog rabies in Central and West Africa

INTRODUCTION: Canine rabies is the main cause of human rabies and is globally responsible for approximately 59 000 human deaths per year, nearly all occurring in low- and middle-income countries (LMICs). It is well known that mass dog vaccination is a cost-effective, sustainable measure to eliminate the disease at its source and prevent human exposure. However, implementation of vaccination campaigns in LMICs and maintenance of disease freedom in targeted regions remain highly challenging. It has been recently demonstrated, that two dog vaccination campaigns were sufficient to interrupt dog rabies transmission in N’Djamena, the capital city of Chad in Central Africa. Unfortunately, canine rabies reappeared a few months after the end of the second campaign, suggesting that reintroduction may be due to influx of infected dogs from neighboring areas, which may be driven by human-mediated dispersal. It is also probable, that such rabies diffusion mechanism exists at larger scales, i.e. country level, and that transboundary exchanges occur. In addition to the role of humans in rabies spread, it is known that landscape features, such as rivers, mountains or deserts can act as natural barriers to disease spread. However, the precise mechanisms for rabies diffusion in dogs at both country level and interregional scale need to be further explored and in consideration of environmental and epidemiological parameters. The aim of this research project is to analyze dog rabies diffusion in Central and West Africa by combining landscape epidemiology with virus genetics. METHODS: phylogenetics and phylodynamics will be first elaborated for Central Africa with the analysis of animal rabies samples, which were recently collected in urban and rural areas of Chad, Cameroon, Central African Republic, Nigeria and the Democratic Republic of Congo. These analyses will be based on the full-length genome sequence, obtained by next generation sequencing (Illumina technology) with a dedicated bioinformatic workflow (implemented on the Galaxy platform). Based on this large dataset, Bayesian phylodynamic inferences will be conducted and the evolution of dog rabies virus will be estimated. In addition, patterns and drivers of virus spread will be determined and environmental and epidemiological factors from different local contexts will be included in the analyses. In the near future, we plan to expand our approach to West Africa, with the inclusion of Mali, Cote d’Ivoire and Liberia. RESULTS: it is expected that the combination of phylogenetic and phylodynamic analyses with landscape epidemiology will improve the resolution of surveillance in the selected African countries and contribute to understanding the geographical distribution and transboundary spread of the disease. We expect to identify main routes of virus transmission. CONCLUSION: the generated knowledge will be further used for the placement of appropriate vaccine barriers and surveillance points and for the planning of dog vaccination campaigns in selected partner countries. Our approach is in line with the overarching aim to eliminate canine-mediated human rabies in Central and West Africa by 2030.