title: Revealing the Micro-scale Signature of Endemic Zoonotic Disease Transmission in an African Urban Setting.
abstract: The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui.
authors.affiliation: Institut Pasteur, Unit Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bourhy
authors.affiliation: Institut Pasteur de Bangui, Bangui, République Centrafricaine.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nakouné
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom.|Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hall
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.|Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Pierre
authors.initials: P
authors.lastname: Nouvellet
authors.affiliation: Institut Pasteur, Unit Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lepelletier
authors.affiliation: Institut Pasteur, Unit Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Paris, France.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Talbi
authors.affiliation: INSERM, UMR 1181 and Institut Pasteur, B2PHI, Paris, France.|Faculté de Médecine Paris Ile de France-Ouest, Université de Versailles-Saint-Quentin, Versailles, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Watier
authors.affiliation: Marie Bashir Institute for Infectious Diseases & Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, Sydney, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.|Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.|Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Cauchemez
authors.affiliation: Rega Institute, KU Leuven, Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.|Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom.|Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
mesh_terms: D000818:Animals; D002488:Central African Republic; D018562:Disease Transmission, Infectious / Q000662:veterinary*; D004283:Dog Diseases / Q000821:virology*; D004285:Dogs; D006801:Humans; D010802:Phylogeny; D011818:Rabies / Q000635:transmission / Q000662:veterinary*; D011820:Rabies virus / Q000235:genetics*; D014505:Urban Population; D015047:Zoonoses / Q000635:transmission / Q000821:virology*