How Sequencing Technology Helped Tackle the Last Ebola Outbreak

A well-funded virologist armed with next-gen genetic sequencing technology was able to help track the spread of Ebola in Sierra Leone with unprecedented speed.

Brian Buntz

Ian Goodfellow, a virologist at the University of Cambridge, was shaken by a flurry of press attention the Ebola crisis was receiving in 2014. "I will never forget a New York Times article describing just how bad things had gotten in Sierra Leone's second-largest city of Makeni," he said. The article showed a picture of a four-year-old lying on a hospital floor covered in body fluids.

"At that point, I made a decision to get involved," Goodfellow recounts. "It wasn't an easy decision to make and it wasn't easy to make it with my wife who is a virologist as well."

Goodfellow has a friend who works for the CDC that sent a picture of what conditions were like on the ground during the outbreak. "My wife made me make a will before I left. But I felt like I really had to go," he recalls. "The diagnostics portion was easy for me to do and working in the laboratory is quite safe. I was less confident of my ability to stay safe outside of the laboratory. You don't know what you are going to be exposed to."

Ultimately, more than 11,000 people in Western Africa died before the World Health Organization declared Western Africa free of Ebola last year. But now, more than 100 people have potentially been exposed to the virus in a new outbreak in Sierra Leone.

The latest outbreak illustrates how easy it is for the epidemic to flare up again, but Goodfellow also notes that technology has evolved to the point that Ebola can be theoretically contained fairly easily--an observation that proved to be especially frustrating given the slow response to the most-recent widespread epidemic.

When Goodfellow went to Sierra Leone in 2014, he sought about setting up a diagnostic lab. He became interested in working with genetic sequencing technology when he realized that it was poorly understood how the virus was evolving. "Everyone was concerned that it could spread by aerosol transition or possibly become more virulent. We were in unknown territory," he recounts.

While some scientists were using sequencing to understand the disease, that involved shipping samples outside of the country. It often took months for the results to come back and researchers at organizations like the WHO, the Ministry of Health, or CDC didn't have access to the data regarding how the virus was evolving.

Goodfellow's group decided to get a sequencer into Sierra Leone. "I naively tried to do it. I had never run one before. I had never worked in Africa, never with Ebola, never in a laboratory inside of a tent," he recounts. "But I thought: how hard can these things be?"

Eventually, sequencing technology from Thermofisher was airlifted to Goodfellow's group and was set up inside of a laboratory in a tent. The technology is still in use in Sierra Leone.

It helped that the sequencer in question, the Ion PGM semiconductor-based next-generation sequencing was both relatively easy to use and capable of withstanding Sierra Leone's heat.

By contrast, Thermo Fisher's Ion Torrent semiconductor-based sequencing technology relies on a simple semiconductor chip (measuring about 1 x 1 in., see image below), on which the DNA sequencing process takes place. "Ion Torrent's semiconductor technology enables Dr. Goodfellow's work in two key areas; robustness and simplicity of operation," explains Andy Felton, vice president of product management for Thermo Fisher. Unlike traditional sequencing platforms that require complex and motion and temperature sensitive optics, Ion's platform uses the same CMOS technology that's used in iPhone cameras as its basic detection system, Felton notes. "The semiconductor chips detect minute changes in pH and require only and instrument with simple and very robust fluid delivery system and no complicated and sensitive optics to perform sequencing. This enables the platform to be shipped to and operated easily with excellent reliability."

Chris Linthwaite, president of Genetic Sciences at Thermo Fisher Scientific explains the basic steps of using the technology: "You take a blood sample, you do a purification and sample prep, and then you do a library prep step, and then you do deep sequencing on the RNA. You are looking for on the informatics-side of strain drift." While polymerase chain reaction (PCR) technology can be used for Ebola screening, sequencing is more effective, Linthwaite says.

Genomics technology, in general, is a powerful tool for investigation. "You can look where the origin is or the chain of custody and who it has passed through. It can be used as an investigation tool to do traceback studies. This is like forensics of viruses. As you sequence others, it can begin to identify trace background DNA from the host," Linthwaite says. "So you can identify fragments of legacy DNA that they have collected from various hosts. You can put together a jigsaw puzzle."

"When you come up with a certain sequence, you can link informatically to the CDC's database. If you have a match and have a bridge into the CDC database, you can have access to a rich depth of information," Chris Linthwaite says.

During the epidemic, Goodfellow worked to determine how the infection was being transmitted. "There have been a number of cases where no one has an idea of how they got infected. By sequencing the virus and comparing it with all of the viruses we and other people have sequenced, we can find the next closest match and we can say your virus came from this person," Goodfellow explains. "We have cases of sexual transmission where male survivors can maintain the virus in their semen for 9 months."

Goodfellow recounts another example of a case linked to a hospital that had been under quarantine for 21 days. "That time frame is the longest recorded period from symptoms to exposure," Goodfellow says. "At day 23 after the quarantine, a child died and tested positive for Ebola." Researchers were concerned that the incubation period was getting longer. "That would have a huge impact and the quarantine would have to be 25 days," Goodfellow recounts. "It turned out that the child was being breastfed and the lady never presented with symptoms. So we sequenced the virus in the breast milk and the child," he says. "She didn't report any symptoms. She was infected but had the virus and passed it on to the baby." So in this case, the researchers were able to determine that incubation period wasn't getting longer.

Having genetic sequencing data be available so quickly had not been possible in the past. Traditionally, it took anywhere from three to five months to get results back, and, at that point, the information was no longer completely pertinent because of the virus is constantly evolving. The value of the data is much greater when it is available within three days of an outbreak as opposed to three months or more. "The technology was enabling us to sequence viruses as they were appearing. Many people hadn't done that before."  

In the end, a full-blown Ebola outbreak remains a possibility. Ebola is always in the environment somewhere.

One of the main challenges in containing it is that it has traditionally been poorly understood. There are barriers in terms of lack of education and lack of trust in scientists. "Many locals didn't know what a virus was and many of them had never been to a hospital before," Goodfellow says. "They were used to going to healers." Yet education is important in containing infectious diseases.

Technology and having experienced researchers available could help curtail future outbreaks, however. "Should someone present with the same symptoms again, you need people who are trained in laboratory and have the facilities to test for them quickly," Goodfellow says. "It is a combination of education, training to run diagnostic facilities, and providing resources and international back up. People in countries like the United Kingdom and the United States need to get involved before it explodes."

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