Liana Kafetzopoulou, is a NIHR HPRU PhD student based at Public Health England (PHE), working on metagenomic (non-targeted) sequencing for viral pathogens. Liana’s initial work concentrated on lab-based metagenomic analysis of Chikungunya and Dengue virus, where she demonstrated that nanopore sequencing can elucidate full viral genomes from a relevant range of viral titres. Rapid and unbiased identification methods, such as metagenomic sequencing, can be vital for the identification and characterisation of emerging pathogens for which little prior knowledge is available; thus the next step was to test the approach in the field, with a more divergent virus.
A collaboration was set-up with the Bernhard Nocht Institute for Tropical Medicine and a team, including Liana, travelled to the Institute of Lassa Fever Research and Control in Nigeria, a remote and resource-limited location, to sequence Lassa virus. Lassa is a haemorrhagic fever virus typically found in West Africa and endemic in Nigeria transmitted through contact with infected rats.
The in country team included: Sophie Duraffour (Team Lead), Liana Kafetzopoulou, Anke Thielebein and Julia Hinzmann. The team worked in parallel with an offsite team that included: Steve Pullan (PHE Porton Down) and Philippe Lemey (KU Leuven, Belgium).
In February 2018, during the time the team were on the ground, the largest number of recorded Lassa fever cases in Nigeria was reported. The unprecedented number of cases raised fears of the emergence of a strain with a higher rate of transmission. Due to these concerns, on February 28th the NCDC and the WHO urgently requested sequencing information and preliminary results from the teams pilot-scale study, which employed in-country, mid-outbreak, viral genome sequencing directly from clinical samples using a metagenomic approach on the Oxford Nanopore MinION device (Oxford Nanopore Technologies, Oxford, UK).
This instigated a major upscale in sequencing efforts leading to sequencing of 120 samples and the team were able to set up the field lab, develop and establish a sequence analysis workflow and deliver complete genomic analysis of 35 samples during their stay in-country. Phylogenetic analysis of the L and S segment of the Lassa virus genome indicated that the outbreak was due to independent spill-over from the rodent reservoir and that there was no evidence of human-to-human spread.
The conclusions drawn from the first set of genome sequences released, immediately removed fears of the emergence of a novel strain and allowed public health resources to be allocated appropriately.