Routinising genomic surveillance for endemic zoonoses: from rabies control to elimination

Kirstyn Brunker (University of Glasgow, United Kingdom) began her talk by introducing zoonoses: diseases that can be transmitted from animals to humans. She noted that 60% of existing and 70% of emerging human infectious diseases are zoonotic. She described how endemic zoonoses present a huge disease burden year on year, predominantly affecting the most disadvantaged communities in low or middle-income countries, but are neglected by national policy makers. With renewed focus on such zoonoses and the latest surveillance technology, Kirstyn stressed how there is an opportunity to work towards controlling them, possibly eliminating them, and ensuring preparedness for future zoonotic events.

Rabies, the world’s deadliest disease, is one such endemic zoonosis. It is caused by an RNA virus which can infect all mammals, and is nearly 100% fatal once symptoms appear; nearly all human cases are caused by bites from domestic dogs. Rabies kills over 59,000 people each year, but is 100% vaccine-preventable. A campaign led by WHO now aims to eliminate dog-mediated rabies globally by 2030 – Kirstyn described surveillance as ‘crucial’ to this goal. The 12 kb viral genome makes it relatively easy to sequence, but most cases of rabies occur in low/middle-income countries with limited sequencing capacity. However, Kirstyn highlighted how ‘genomics is now more accessible than ever’ thanks to lower costs and accessible platforms such as the MinION. Kirstyn and her team have been able to produce a deployable ‘lab-in-a-suitcase’, to enable rabies virus to be sequenced anywhere, including in low-resource settings. Previous sequencing of rabies virus has revealed a wealth of information, including discrimination of host variants – important in assessing the threat from wildlife variants – and analysis of periods of ‘epidemiological silence’, to determine whether any cryptic transmission has been missed by surveillance.

Kirstyn and her colleagues set about creating an accessible genomic surveillance platform which could be used in areas affected by rabies to build capacity for rabies sequencing in these regions. This comprised a sample-to-sequence pipeline using the ARTIC Network tiled amplicon approach, plus training to improve local genomics expertise. The platform was designed to enable both cost-effective, bulk sequencing of archived samples - to provide contextual information - and the rapid sequencing of new rabies cases, to provide actionable information where and when it was needed. The ‘lab-in-a-suitcase’ has been used in Peru, Kenya, and the Philippines, and has been deployed in a range of environments, from a public health lab to the back of a car.

Kirstyn then described the insights enabled by this work. In East Africa, rabies is endemic, despite vaccination efforts and its low R₀. Prior to their portable platform, samples were exported to the UK, commonly resulting in a sample-to-sequence time of 3-6 months. With the MinION, this can now be performed in-country in 1-2 days. This data has revealed that large, susceptible dog populations and human-mediated dispersal drive the co-circulations of lineages and frequent re-introductions. She noted that the pattern is repeated locally and nationally, and that frequent extinction and re-introduction of lineages were a common theme, with implications for control efforts. The pipeline was also used to investigate an outbreak on Pemba Island, off the coast of Tanzania. After four years of mass dog vaccination, there was a period of epidemiological silence; no cases were detected for a year, but then an outbreak followed in 2016. They sequenced samples from before and after the outbreak, and through analysis of the lineages present, identified multiple introductions from the mainland. The study highlighted the importance of continued vaccination and surveillance on the island.

Kirstyn also showed how the sequencing pipeline was used to investigate rabies re-emergence in Arequipa, Peru, after 15 years of epidemiological silence. Rapid sequencing of archive samples from 2015-19 was performed on MinION, representing ~25% of detected cases. Combining genomic and spatial information allowed reconstruction of the spread of the virus, revealing that it was introduced from a neighbouring region, Puno, with subsequent rapid spread in the largely unvaccinated dog population. They also hypothesised that certain landscape features were acting as ‘dog highways’, facilitating the spread.

Finally, Kirstyn noted that the rabies sequencing capacity that developed from this project directly facilitated the production of the first SARS-CoV-2 genomes in the Philippines; this work is being presented by Ma. Angelica Tujan in the SARS-CoV-2 breakout at NCM 2020. It has also led to a UKRI-funded project to scale up SARS-CoV-2 sequencing in the Philippines.