Today is the final day of the First International Conference on Lassa Fever. The conference theme is “Lassa Fever at 50,” marking 5 decades since the first identified case in Nigeria in 1969. Last year, Outbreak Thursday published 2 posts on an unusually large Lassa fever outbreak in Nigeria. The first post, from February 2018, worked through some pathogen-specific considerations for the outbreak and commented on “bottom line” protective measures to consider while responding to this surge in cases. Outbreak Thursday followed up in April 2018, providing new case details and considerations for future outbreak control efforts.

A few weeks later, the WHO Regional Office for Africa (AFRO) shared an update after 6 consecutive weeks of reduced Lassa fever cases. This report suggested that the largest outbreak in Nigeria’s history was beginning to come under control, correlating with the transition from the dry to wet season. Our first post outlined how Nigeria’s seasons impact the incidence of Lassa fever, and this difference can be seen in the case counts from 2018. Of the 633 confirmed cases reported in 2018, 125 were reported between May and October, roughly corresponding to Nigeria’s wet season (approximately 20.8 cases per month). By comparison, 423 cases were reported from January to April, during the dry season (approximately 105.8 cases per month). In November and December, Nigeria reported 85 confirmed cases (42.5 per month), and 25 new confirmed cases were reported in just the first week of 2019. If the high case counts return for the 2019 dry season, we could expect to see increasing incidence over the upcoming months.

The second Outbreak Thursday post briefly touched upon the influence of phylogenetic testing during Nigeria’s 2018 Lassa fever outbreak. This process, which was cited in a WHO report, provided public health officials with key information about the strain of Lassa fever affecting new cases, which influenced the direction of the public health response. Earlier this month, Science published an article that discussed the use of metagenomics sequencing during the Lassa fever outbreak. The remainder of this OT post will take a close look at this new piece of outbreak literature and discuss its possible applications to future outbreak response.

Real-time Metagenomic Sequencing and Lassa Fever

The Science article mentioned above discusses how real-time metagenomics sequencing during an infectious disease outbreak can provide public health officials with information that can impact response decisions. In the midst of Nigeria’s 2018 Lassa fever outbreak, it became clear to public health officials that the situation was on pace to surpass expectations set by past outbreaks. This raised concerns that a new strain of Lassa fever had emerged, leading to increased transmissibility in human hosts. To address this new question, the Nigeria Centre for Disease Control (NCDC) and the WHO recruited a team of researchers to sequence the viral genome present in Lassa fever patients.

In early March 2018, a team of researchers flew to Nigeria, equipped with sequencing technology to try and provide answers about the strains of Lassa fever circulating in Nigeria. Using samples from patients in the epicenter of the outbreak, researchers were able to compare newly sequenced genomic information with sequences from the previous year and sequences available through the genetic  sequence database, GenBank. In total, they sequenced 120 samples, and found that a new strain was not responsible for the ongoing outbreak. Rather, spillover from the rodent population appeared to be the driving factor in disease transmission. In addition, they were able to answer questions regarding human-to-human transmission, which had been occurring, but not at a rate of major concern.

It took only 10 days from the NCDC and WHO’s request for this team to arrive in country and provide an preliminary findings of their genomic analysis. This report matched their final conclusions, which gave health officials an immediate sense of relief and direction for response, including the allocation of limited response resources. With the knowledge that the driving factor for the 2018 outbreak was spillover from the rodent population, health officials were able to focus their resources on response efforts that address this particular concern, such as vector control and sanitation.

MinION Sequencing Technology

The researchers used a MinION sequencer from Oxford Nanopore Technologies, a tool that was built to function in areas with limited resources. The MinION sequencer is a small, lightweight device with the ability to transfer sequencing data to standard computers. In practice, this technology allows a team to bring sequencing technology to areas that may not have access to traditional laboratory space or equipment. In addition to addressing certain limitations of field response, there is evidence that supports MinION’s capacity to sequence viral RNA, enabling its use in Lassa fever response. An academic report successfully demonstrated MinION’s ability to sequence viral genomes and expressed that its sequencing technique may circumvent common challenges associated with genomic variability. The variable nature of circulating Lassa virus strains can create a roadblock for several traditional sequencing technologies that require multiple exact sequence matches to effectively identify genome sequences present in specimens.

The scientific community has worked to refine this sequencing technology. When first introduced, several outstanding challenges were shared in academic literature. Researchers have worked to address these remaining questions, and some have tested its wider application in genome sequencing. The case study of metagenomic sequencing in Nigeria reported in Science highlights the positives of this technological advancement. MinION’s small size and ability to function in suboptimal environments makes it a clear choice for real-time outbreak response, and its utility in the outcome of this project demonstrates promise for its use in future outbreak responses.

Moving Forward

This research progresses the potential for future real-time metagenomic sequencing in the response to an infectious disease outbreak. This recent Science article illustrates the usefulness that these real-time efforts can have in outbreak response operations. Modern developments in MinION technology have addressed a number of initial concerns. As the scientific community continues to refine the capabilities of this sequencing technology, it may have a sizeable impact on the practice of outbreak response.

Photo Courtesy of Dr. Yves Robin and Dr. Jean Renaudet, Arbovirus Laboratory at the Pasteur Institute in Dakar, Senegal; World Health Organization, via CDC’s Public Health Image Library.
Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.