Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak

Abstract

Mobile detection of Lassa virus Lassa fever is a hemorrhagic viral disease endemic to West Africa. Usually, each year sees only a smattering of cases reported, but hospitalized patients risk a 15% chance of death. Responding to fears that a 10-fold surge in cases in Nigeria in 2018 signaled an incipient outbreak, Kafetzopoulou et al. performed metagenomic nanopore sequencing directly from samples from 120 patients (see the Perspective by Bhadelia). Results showed no strong evidence of a new strain emerging nor of person-to-person transmission; rather, rodent contamination was the main source. To prevent future escalation of this disease, we need to understand what triggers the irruption of rodents into human dwellings. Science, this issue p. 74; see also p. 30 Mobile nanopore sequencing technology has been successfully used for direct sequencing from hemorrhagic fever patient samples. The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.