21 November 2018

How Real-Time Virus Sequencing Can Help Stop Epidemics?

KONFRONTASI -   Lassa fever is a deadly virus that’s typically transmitted to humans from rodents. Every year, thousands of cases are reported in West Africa, and thousands of people die from the disease.

Earlier this year, an outbreak of Lassa fever began spreading in Nigeria. The virus is not uncommon for the country, but it wasn’t the usual time of year for infections, and the number of people contracting the disease appeared to be increasing at a much faster rate than prior outbreaks. Responders began to ponder worst-case scenarios: Was this a new, more potent strain of the virus? Was it spreading from person to person?

In a new study published Wednesday in the New England Journal of Medicine, researchers outline how an ongoing partnership between scientists at Irrua Specialist Teaching Hospital and Redeemer’s University in Nigeria and researchers at the Broad Institute of MIT and Harvard allowed for real-time sequencing of virus samples to help with the outbreak response. One of the study’s first authors, Katie Siddle, PhD, a postdoctoral fellow in the Sabeti Lab at the Broad Institute, talked to Medium about the findings and what the implications are for future epidemics.

Medium: What was the overarching motivation for your study?

 In early 2018, it became apparent that cases of Lassa fever were well above what is usual for this time of year; however, it wasn’t clear why there was such an increase compared to previous years, and many worrying questions were unanswered. In particular, was this a new, more virulent strain of the virus, or was the virus transmitting more frequently between humans? In discussions with colleagues at Irrua Specialist Teaching Hospital (ISTH) — one of the diagnostic and treatment facilities at the forefront of the outbreak — and at Redeemer’s University, we felt that genomics was uniquely positioned to provide insight to these pressing questions.

Your teams were able to pull this off in real time. How was it possible? Why was timing critical?

For many years, we have been investing in building capacity for viral genomics in Nigeria at the African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer’s University. Through extensive training and the development of technologies, we have built the infrastructure and expertise to perform this work in Nigeria. This meant we were positioned to rapidly generate and share data from the first batch of samples. It was important that these findings were known quickly, as any changes in the viral genome or in its transmission could have had implications for the effectiveness of public health interventions to deal with the increase in cases.

What did you find?

The first batch of samples suggested that the Lassa virus genomes in patients from 2018 were not from a new or “mutant” strain. These viruses were genetically more similar to genomes from other patients from the same geographic region from previous years than they were to each other. This further suggested that these were not cases of human-to-human transmission.

These results were confirmed with a much larger data set generated during and after the outbreak. This gave us a high-resolution picture of the diversity of Lassa virus in Nigeria. In particular, we were able to combine this with geographic information about the cases and suggest that the geographic structure of this diversity is delineated by Nigeria’s two major rivers — the Niger and the Benue. We could also infer the age of Lassa virus strains in these regions. Intriguingly, in the southwest, where Lassa is most prevalent today, the common ancestor of all sequences was younger than elsewhere, suggesting it may have been more recently introduced in this area.

Why was this important for the outbreak response?

Our initial findings were shared in real time with the Nigerian CDC (Centers for Disease Control) and others and helped to alleviate concerns about the role of human-to-human transmission or a new or more virulent strain in driving the increase in cases. This knowledge helped guide the public health response to the outbreak.

“From each outbreak, we take away lessons that help us learn and, hopefully, respond better.”

Lassa fever is a very serious infectious disease. How might your study affect future outbreaks, whether caused by Lassa or other viruses?

We believe this work is a model for the value of local genomic surveillance and response to outbreaks. Lassa fever is endemic to Nigeria, with a peak in cases occurring each year during the dry season. As the next Lassa season approaches, we are expanding our sequencing work in Nigeria to monitor the virus and detect any changes in its genome, as well as other circulating viruses that cause similar symptoms.

The genomes analyzed in this study are also helping us design improved diagnostics for Lassa virus. Lassa is very genetically diverse, which makes designing sensitive diagnostics challenging. For example, we are currently using these genomes to develop optimized guides for a CRISPR-based diagnostic tool that could be a low-cost alternative to existing methods.

The techniques we used in this study were not specific to Lassa virus, though. This was valuable, as it allowed us to rule out other viral infections in the cases we tested, and it means that the same approaches are applicable to other viruses and could be readily used elsewhere. Similarly, our software for analyzing the data has been used extensively to study Ebola, Lassa, Zika, and other viruses and is freely available for use in other outbreaks.

There’s an ongoing outbreak of Ebola, another hemorrhagic illness, in the DRC. Could research like yours be helpful? What are we learning from these outbreaks?

Since the West African Ebola outbreak in 2014–16, the value of genomic data in outbreak situations is becoming increasingly recognized. In the case of the DRC outbreak, genomics can tell us whether the Ebola virus looks like the viruses previously observed in the DRC or was introduced from another region, which could help inform control measures. There have been some insights from genome sequencing from this outbreak: A preliminary report suggested that the outbreak in North Kivu was genetically distinct from that in Equateur in May 2018, and more information is eagerly anticipated to better understand this outbreak.

From each outbreak, we take away lessons that help us learn and, hopefully, respond better. In Nigeria, the Nigerian CDC recognized quickly the importance of genomic data and what it could bring to their response. Moreover, we believe this work underscores the importance of building local capacity for data generation and analysis as well as strong partnerships so that regions at higher risk for outbreaks, like Nigeria, can be better prepared to respond.(Jft/Medium)

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