Complex Epidemiology of a Zoonotic Disease in a Culturally Diverse Region: Phylogeography of Rabies Virus in the Middle East

Abstract

The Middle East is a culturally and politically diverse region at the gateway between Europe, Africa and Asia. Spatial dynamics of the fatal zoonotic disease rabies among countries of the Middle East and surrounding regions is poorly understood. An improved understanding of virus distribution is necessary to direct control methods. Previous studies have suggested regular trans-boundary movement, but have been unable to infer direction. Here we address these issues, by investigating the evolution of 183 rabies virus isolates collected from over 20 countries between 1972 and 2014. We have undertaken a discrete phylogeographic analysis on a subset of 139 samples to infer where and when movements of rabies have occurred. We provide evidence for four genetically distinct clades with separate origins currently circulating in the Middle East and surrounding countries. Introductions of these viruses have been followed by regular and multidirectional trans-boundary movements in some parts of the region, but relative isolation in others. There is evidence for minimal regular incursion of rabies from Central and Eastern Asia. These data support current initiatives for regional collaboration that are essential for rabies elimination. Despite being one of the oldest recognised infectious diseases, rabies continues to cause thousands of preventable human deaths per year. As a zoonotic disease, control of infection in the reservoir has been proven the most efficient route to reduction of human cases. In some regions, the epidemiology is well understood, with either dogs or wildlife known to be the primary reservoir and with little or no movement from, or into other regions. This is not the case in the Middle East, where rabies is underreported in animals and humans, there is little laboratory confirmation of infection, and the extent of rabies spread from country to country is not known. Previous studies have demonstrated trans-boundary movement of rabies but have been limited by a low number of available samples from some countries, and the direction of spread has been difficult to estimate. Here we use rabies virus partial genome sequences of 183 viruses from over 20 countries, combined with geographical and temporal information, to reconstruct the evolution of rabies viruses circulating in the Middle East. The results reveal an apparent barrier to spread between some regions but regular movement between others. These analyses will support policy on rabies control by indicating the relative importance of local control and animal movement restrictions when allocating resources.