Phylogeography of foot-and-mouth disease viruses in Equatorial Africa

Project offered for Ker Memorial PhD Studentship in Infectious Diseases

Foot-and-mouth disease (FMD) remains the most important global livestock disease, affecting livestock health, global trade and livelihoods. Controlling FMD in Equatorial Africa (EqA) would improve livelihoods and reduce this threat to global livestock production and trade.

 FMDv is RNA virus of the Picornaviridae family. Its genome encodes information for 4 capsid proteins (VP1-4) and several non-structural proteins. Based on the level of cross protection between strains, the virus can be divided into seven serotypes, which are clinically indistinguishable but which have different epidemiologies. The most common route of infection for a new host is by direct contact with an infected animal or indirectly through contact with contaminated surfaces or products, such as personnel or vehicles. Markets and mixing at watering points allows close contact between herds and wildlife facilitating spread, while spread of FMD over larger scales is mainly through movement of animals and contaminated animal products.

EqA remains a source region of FMDv with a complex epidemiology due to multiple circulating serotypes, currently O, A and all three SATs. The importance of EqA has been recently highlighted with the spread of a SAT2/XIV strain, not reported for over a decade in Africa, into central Asia. The lack of surveillance in “endemic” countries leaves a huge knowledge gap in our understanding of FMDv circulation and persistence which hampers the timely deployment of appropriate vaccines. This is further complicated by the growing understanding that “endemic” FMD is in reality repeated epidemic waves of different serotypes/strains.

The aim of this project is to work with the national ministries of agriculture in key countries in EqA where we have strong links and support the collection, processing and sequencing of spatio-temporally located samples. We have recently demonstrated a simple swabbing method of sampling that can be used to generate whole genomes and also the use of environmental samples from markets or infected farms where we were able to recover partial genomes of FMDv using the ONT MinION™. These approaches require much less effort and less restraint of the animal than collection of epithelium from lesions and virus culture.

This PhD project will pilot transfer of our newly developed sampling approach, our novel primer sets for pan-serotype unbiased sequencing to government vets along with digital data capture tools to geolocate outbreaks in time and space. The aim is to generate data on outbreaks in space and time over 2 years that will have linked whole genome sequence data to carry out a range of analyses including basic descriptive study of diversity of serotypes and strains, evolution clock rate estimation, and relatedness to available sequences from across the region with time-based phylogenetic trees. The student will then use general linear models to test the role of trade networks and landscape characteristics in explaining the observed directionality and velocity of viral dispersion at regional scales. They will also quantify trans-regional spread and processes that underpin geographic structuring of viral genetic diversity at the continental scale, including factors that contribute to large-scale phylogeographic clustering of viral diversity (viral “pools”) across EqA to understand the scale at which FMDv persists.

Training and skills

The student will gain a very broad training in molecular epidemiology and phylogenetics. They will get experience of surveillance and sample collection, storage and processing in the field. They will gain experience of qPCR and mobile sequencing technology on the ONT MinION™ platform along with the bioinformatics pipelines. Finally, they will gain experience of analysis of phylogenetic data and the use of BEAST to develop time rooted phylogenetic trees and model the spatiotemporal spread of FMD virus strains.