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

Abstract

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 WHO to inform the public health response. Real-time analysis of 36 genomes, and subsequent confirmation using all 120 samples sequenced in-country, revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events; allaying concerns of an emergent strain or extensive human-to-human transmission.

Applications of sequencing technology in clinical microbial infection

“…Due to the above advantages, Nanopore sequencing technology has been widely used in the field of epidemic outbreak investigation over the past 2 years to detect infectious pathogens, antimicrobial drug resistance and other infectious areas of concern. For the rapid and real‐time monitoring of outbreaks, researchers conducted real‐time dynamic genomic monitoring of the Lassa fever epidemic in Nigeria and the Guinea Ebola virus epidemic through a small portable Oxford Nanopore MinION device. Through the use of direct RNA sequencing, a team of microbiologist led by John Barnes of the US CDC sequenced the complete RNA genome of the influenza A virus using Nanopore .…”

Vaccine platforms for the prevention of Lassa fever

“…VSVΔG/LASVGPC has yet to be tested for efficacy against these isolates [29,30]. Nevertheless, these data support the feasibility of effectively protecting against multiple LASV lineages with a single vaccine.…”

“…During a 2014 outbreak of Lassa fever at tertiary hospitals in Ebonyi and Enugu in southeastern Nigeria, phylogenetic analysis of patient isolates provided strong support for the role of virus transmission between infected individuals [27]. The dramatic increase in cases during the 2018 Nigerian Lassa fever season launched investigations into the possible emergence of a new strain with a higher transmission rate [28,29]. Two sequencing studies, analysing 220 and 120 LASV genomes from infected patients, revealed high variability and derivation from previously circulating viruses rather than from a single dominant strain [29,30].…”

“…The dramatic increase in cases during the 2018 Nigerian Lassa fever season launched investigations into the possible emergence of a new strain with a higher transmission rate [28,29]. Two sequencing studies, analysing 220 and 120 LASV genomes from infected patients, revealed high variability and derivation from previously circulating viruses rather than from a single dominant strain [29,30]. The data did not indicate phylogenetic clustering of LASV from samples collected at similar time points, which would be expected in the event of increased human-to-human transmission.…”

“…The data did not indicate phylogenetic clustering of LASV from samples collected at similar time points, which would be expected in the event of increased human-to-human transmission. Therefore, Lassa virus transmission continues to principally occur via independent cross-species transmission events [29,30]. No clear reason for the increase in Lassa fever cases has been found; changes in the distribution of the rodent reservoir population or improved disease diagnosis and surveillance remain possible explanations [30].…”