title: Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing.
abstract: Many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. Phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. Increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. Here, whole-genome variation was used to uncover fine-scale population structure in endemic canine rabies virus circulating in Tanzania. This is the first whole-genome population study of rabies virus and the first comprehensive phylogenetic analysis of rabies virus in East Africa, providing important insights into rabies transmission in an endemic system. In addition, sub-continental scale patterns of population structure were identified using partial gene data and used to determine population structure at larger spatial scales in Africa. While rabies virus has a defined spatial structure at large scales, increasingly frequent levels of admixture were observed at regional and local levels. Discrete phylogeographic analysis revealed long-distance dispersal within Tanzania, which could be attributed to human-mediated movement, and we found evidence of multiple persistent, co-circulating lineages at a very local scale in a single district, despite on-going mass dog vaccination campaigns. This may reflect the wider endemic circulation of these lineages over several decades alongside increased admixture due to human-mediated introductions. These data indicate that successful rabies control in Tanzania could be established at a national level, since most dispersal appears to be restricted within the confines of country borders but some coordination with neighbouring countries may be required to limit transboundary movements. Evidence of complex patterns of rabies circulation within Tanzania necessitates the use of whole-genome sequencing to delineate finer scale population structure that can that can guide interventions, such as the spatial scale and design of dog vaccination campaigns and dog movement controls to achieve and maintain freedom from disease.
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK; The Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G12 8QQ, UK; Animal and Plant Health Agency, Weybridge, Woodham Lane, KT15 3NB, UK.
authors: Kirstyn
authors: K
authors: Brunker
authors: Animal and Plant Health Agency, Weybridge, Woodham Lane, KT15 3NB, UK.
authors: Denise A
authors: DA
authors: Marston
authors: Animal and Plant Health Agency, Weybridge, Woodham Lane, KT15 3NB, UK; School of Veterinary Medicine, University of Surrey, Guildford GU2 7XH, UK.
authors: Daniel L
authors: DL
authors: Horton
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK; The Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Sarah
authors: S
authors: Cleaveland
authors: Animal and Plant Health Agency, Weybridge, Woodham Lane, KT15 3NB, UK.
authors: Anthony R
authors: AR
authors: Fooks
authors: Department of Veterinary Medicine and Public Health, Sokoine University of Agriculture, Morogoro, United Republic of Tanzania.
authors: Rudovick
authors: R
authors: Kazwala
authors: Tanzania Veterinary Laboratory Agency, Dar es Salaam, United Republic of Tanzania, Temeke Veterinary, Mandela Road, P.O. BOX 9254.
authors: Chanasa
authors: C
authors: Ngeleja
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK; The Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Tiziana
authors: T
authors: Lembo
authors: Ifakara Health Institute, Ifakara, United Republic of Tanzania, P.O. Box 53.
authors: Maganga
authors: M
authors: Sambo
authors: Ifakara Health Institute, Ifakara, United Republic of Tanzania, P.O. Box 53.
authors: Zacharia J
authors: ZJ
authors: Mtema
authors: Ifakara Health Institute, Ifakara, United Republic of Tanzania, P.O. Box 53.
authors: Lwitiko
authors: L
authors: Sikana
authors: MRC Centre for Virus Research, University of Glasgow, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors: Gavin
authors: G
authors: Wilkie
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK; The Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Roman
authors: R
authors: Biek
authors: Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow G12 8QQ, UK; The Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Katie
authors: K
authors: Hampson
keywords: RNA virus; endemic; phylodynamics; rabies; translocation; zoonoses