Abstract
Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries.
Highlights
Surveillance is critical to inform infectious disease management and control programmes (Klepac et al, 2013; Molyneux et al, 2004) and genomic data is emerging as a powerful new surveillance tool (Cotton et al, 2018)
Pathogen sequencing has become increasingly routine in well-resourced public health laboratories, but in low- and middle-income countries (LMICs) where most emerging and endemic zoonoses occur, sequencing capacity is more limited and the direct application of genomics-informed surveillance is still at an early stage (Balloux et al, 2018; Folarin et al, 2014; Gardy & Loman, 2018)
Through a series of sequencing applications and trainings conducted in different settings between 2017–2019, we demonstrate the feasibility of a cost-effective, in-country pipeline for whole genome sequencing (WGS) of rabies viruses (RABV) using the MinION
Summary
Surveillance is critical to inform infectious disease management and control programmes (Klepac et al, 2013; Molyneux et al, 2004) and genomic data is emerging as a powerful new surveillance tool (Cotton et al, 2018). There is potential to extend genomic technologies to endemic pathogens such as rabies, foot-and-mouth disease, brucellosis and bovine tuberculosis, which are responsible for major impacts on people’s health and livelihoods on a daily basis (Cleaveland et al, 2017; Danielsen et al, 2019; Halliday et al, 2015) Such an approach could reduce the lag time from sample to sequence and epidemiological action that is typical for these neglected diseases, while simultaneously building genomic capacity in LMICs. Investing in the surveillance of these endemic pathogens builds core capacities necessary for the detection of unusual disease emergence events that precede epidemics (Cleaveland et al, 2017; Halliday et al, 2017)
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