Tracking a duo of deadly diseases

Pardis Sabeti-Big 3

June 30, 2015 — Should we be worried about Lassa fever, the hemorrhagic fever that recently killed a New Jersey man? How is it different from Ebola? Computational biologist Pardis Sabeti—recently named a Howard Hughes Medical Institute Investigator for 2015—studies the genetics of both Lassa and Ebola. Here she discusses the nature of these viruses and her efforts to guide intervention strategies.

A New Jersey man died from Lassa in May, prompting a scare in the U.S. Subsequent media articles suggested that Lassa is much less deadly than Ebola and doesn’t spread as easily. But you noted in a December 2014 New York Times article that Lassa “likely kills tens to hundreds of thousands of people every year,” and the article also said that only 16% of those admitted to hospitals in the country of Sierra Leone with Lassa survive. Can you clarify the threat from this virus—both in the U.S. and in Africa?

It is very important to make the distinction between what we call the “case fatality rate” and the overall fatality rate of a virus. A “case” is an individual who becomes sick with an infection and presents at the hospital. The crucial distinction is this: The fatality rate for all who are infected with Lassa virus may be quite low, but for those who come to the hospital with Lassa—the “cases”—the fatality rate is quite high. In Sierra Leone, the current case fatality rate is around 70% but the overall fatality may be much lower. It is likely that there are many individuals with a low level of infection who never come to the attention of the hospital and may not even show any sign of the disease.

Why do some people succumb while others don’t? We know that different virus microbes have very different outcomes. For example, some individuals cannot become sick with HIV, while others can have very rapid and devastating outcomes. All virus microbes have a different kind of reaction within each person. There also may be many people who have pure resistance to viruses; for example, there may be people infected with Lassa who don’t have symptoms and thus don’t come to the attention of health professionals.

Still, we should be concerned about both Lassa and Ebola. These are both viruses that can show very high case fatality rates across a large number of individuals. Each of these viruses has features that make them potential bioterrorist threats. So while most strains of Lassa and Ebola may not be a threat, there could be versions of the virus with the potential to be quite deadly. The sooner we develop good diagnostics, treatments, and vaccines for them, the better off all of us will be.

How might your work on Lassa and Ebola lead to better control—and fewer deaths—in the event of an outbreak?

The work that we do both on Lassa and Ebola is focused on understanding the genome sequence of these viruses. The genome of a virus, or any organism, is the blueprint that encodes its biological properties. Since most diagnostics, vaccines, and therapies are developed based on the genome sequences of these viruses, it’s critical to have this information—and that’s what we produce. We can also use this information to study important properties of the virus. The evolution of the virus, its epidemiology, the way that it’s transmitted, and the level of exposure are all important answers that genomics can help provide.

You have a new paper out in Cell that describes how, using genome sequencing, you and your colleagues were able to shed light on how the Ebola virus evolved genetically during the latest outbreak. What is the most important takeaway from this paper?

Our early work on Ebola tracked how the virus emerged within the first three weeks of the documented outbreak in Sierra Leone in May 2014, showing that, as the virus spread from human to human, new mutations were emerging but few were being weeded out. Now, by tracking the virus from December 2014 through May 2015, we see sustained human-to-human transmission and we see the virus weeding out mutations that might not be beneficial to it. The important takeaway is that the virus is beginning to evolve in the manner of an endemic human pathogen. We need to shut that down immediately.

In addition, the genomic data we’ve gathered allows us to trace the epidemiology and transmission of the virus. In that regard, one important finding is that we can show that there has been very little cross-border importation or exportation of the Ebola virus between Sierra Leone and neighboring countries since the implementation of border controls. That’s really important, because it confirms that border control efforts were effective at stopping the virus from crossing between countries.

We also pointed out in the paper that, during dangerous outbreaks of viruses or diseases, it’s critical for researchers to share data as soon as it becomes available. I am deeply passionate about this idea. When an outbreak is so fast moving, and so volatile, we can’t allow for just one individual or group to hold data and work on it. We need many individuals working in parallel. As we generated our data, we made it immediately available, and we saw the ramifications. People used our data in real time to work on diagnostics, vaccines, therapies, and surveillance. Numerous papers, new discoveries and diagnostics were created out of it. Of all of the things we achieved, I think that is what we are most proud of.

Karen Feldscher