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Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology

Genomic data can be used to track the transmission and geographic spread of infectious diseases. However, the sequencing capacity required for genomic ...

University of Glasgow

University of Nairobi, Institute of Tropical and Infectious Diseases

Tanzania Industrial Research Development Organization

Ifakara Health Institute

Katie Hampson and colleagues describe their experience of developing and deploying a large-scale rabies surveillance system based on mobile phones in southern Tanzania.

Mobile Phones As Surveillance Tools: Implementing and Evaluating a Large-Scale Intersectoral Surveillance System for Rabies in Tanzania.

A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project. Bite exposures declined, particularly in the southernmost districts with the smallest dog populations, and health workers successfully transitioned from primarily intramuscular administration of PEP to intradermal administration, resulting in major cost savings. However, even with improved PEP provision, vaccine shortages still occurred in some districts. In laboratory diagnosis, there were several logistical challenges in sample handling and submission but compared to the situation before the project started, there was a moderate increase in the number of laboratory samples submitted and tested for rabies in the project areas with a decrease in the proportion of rabies-positive samples over time. The project had a major impact on public health policy and practice with the formation of a One Health Coordination Unit at the Prime Minister's Office and development of the Tanzania National Rabies Control Strategy, which lays a roadmap for elimination of rabies in Tanzania by 2030 by following the Stepwise Approach towards Rabies Elimination (SARE). Overall, the project generated many important lessons relevant to rabies prevention and control in particular and disease surveillance in general. Lessons include the need for (1) a specific unit in the government for managing disease surveillance; (2) application of innovative data collection and management approaches such as the use of mobile phones; (3) close cooperation and effective communication among all key sectors and stakeholders; and (4) flexible and adaptive programs that can incorporate new information to improve their delivery, and overcome challenges of logistics and procurement.

Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania.

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.

Rapid in-country sequencing of whole virus genomes to inform rabies elimination programmes.

Almost half of all countries in the world are effectively free of human deaths from dog-mediated rabies. But the disease still affects people in low- and middle-income countries, especially the rural poor, and children. Successful regional elimination of human rabies is attributable to advances in significant and sustained investment in dog vaccination, post-exposure vaccination and surveillance, illustrated by productive efforts to reduce human rabies in Latin America over the last 35 years. Nonetheless, countries still facing endemic rabies face significant barriers to elimination. Using the 2017 Global Strategic Plan to end human rabies deaths from dog-mediated rabies by 2030 as a reference point and an organizing framework, we assess progress toward global rabies elimination by examining the characteristics of successful regional control efforts and barriers to elimination. Although substantive barriers exist for countries where rabies remains endemic, advances in knowledge, technology, institutions, and economics provide a basis for optimism.

Human rabies: prospects for elimination.

Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle.

Gurdeep Jaswant

School of Biodiversity,
One Health & Veterinary Medicine,
School of Biodiversity, One Health & Veterinary Medicine

University of Glasgow

Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology

Gurdeep Jaswant

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University of Glasgow

Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology

School of Biodiversity,
One Health & Veterinary Medicine,
School of Biodiversity, One Health & Veterinary Medicine