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Science: Ebola Genomes Provide New Information on West African Outbreak

News, Ebola, Doctor, August 26 2014 Full Size

Augustine Goba, laboratory director at Kenema Government Hospital, diagnosed the first case of Ebola in Sierra Leone. | Stephen Gire

Researchers have sequenced 99 Ebola virus genomes from patients in West Africa, where the largest Ebola outbreak ever recorded is ongoing. Their results, published in the 29 August issue of the journal Science, provide insights into how the Ebola virus entered West Africa — where it had not been found prior to this year — and may guide approaches for improving disease diagnosis and treatment.

"There has never been such an extensive sequencing effort to document viral diversity and evolution during a human outbreak," said lead author Stephen Gire, a research scientist at Harvard University and at the Broad Institute of MIT and Harvard. "It really ushers in a new paradigm of emergency response."

The record number of Ebola sequences his team analyzed were published in a public database. "Because we made these sequences available as we generated them," Gire said, "we have already had a tremendous response from the scientific community." For example, researchers at Scripps Research Institute mapped the sequences to antibodies in the experimental Ebola drug ZMapp, used to treat two Americans at Emory University Hospital earlier this summer, to see if mutations in the 2014 strain fall within important antibody regions that could affect ZMapp's efficacy.

As in all other Ebola outbreaks, the viral strains involved carry distinctive genetic variations. To begin to characterize them, Gire and his colleagues evaluated 99 Ebola virus genomes from 78 patients at Sierra Leone's Kenema Government Hospital.

"The team at Kenema Government Hospital was well-positioned [to do this work]," Gire explained. "They have an excellent clinical laboratory established for treating Lassa fever, another hemorrhagic fever disease similar to Ebola, and so were well-situated to diagnose and monitor Ebola patients."

News, Ebola, Unloading Trucks, August 26 2014 One Third

Stephen Gire delivers laboratory safety equipment and reagents for the Ebola outbreak in Kenema, Sierra Leone. | Nathan Yozwiak

The participating patients were all diagnosed with Ebola between May and June of this year. Their virus samples were transported from the hospital back to the U.S., where Gire and his team sequenced and compared them to genomes from earlier Ebola outbreaks elsewhere in Africa. While previous outbreaks of Ebola were confined to Middle Africa, the 2014 outbreak began in the West African nation of Guinea, later spreading to countries like Sierra Leone, Liberia, and Nigeria.

Through their analyses, the researchers determined when the current outbreak arrived in West Africa. Prior to this, some scientists had suggested that the virus had circulated undetected in animals in the region for decades, but the new sequences reveal that this year's outbreak likely spread from Middle Africa within the last decade.

In previous outbreaks, humans' continual exposure to reservoirs of the virus in animals contributed to outbreak growth. In the current outbreak, however, the genetic data suggest that the outbreak ignited with a single interaction between humans and a viral reservoir in animals.

"It is possible that one animal infected multiple people at the same time," Gire said. Animal meat is often cut into pieces and sold at local markets, he explained, so an infected animal could have been distributed to multiple individuals. "It is also just as possible that one person happened upon a dead animal infected with Ebola…and then passed it to other individuals," he added. "But, there's no evidence in our sequence data that multiple people were exposed to multiple reservoir introductions."

After humans contracted the virus from a single animal reservoir — likely infected fruit bats — it spread through continued human-to-human interaction. Fruit bats are a leading suspect in viral transmission because they have been implicated in human infection by Marburg virus, which is in the same family as Ebola, Gire said. Other fruit bat studies have revealed that some of the animals have antibodies to the Ebola virus in their blood, meaning they were once infected by it.

The current strains of Ebola made their way to Sierra Leone through introduction of two viral lineages from neighboring Guinea.

"I think what was most surprising about our study was that two genetically different viruses were introduced into Sierra Leone at the same time," Gire said, "and likely through one event, a funeral." Gire and his colleagues point to the burial of a traditional healer who had worked with Ebola patients from Guinea as the possible source of one or both Ebola lineages in Sierra Leone.

"This information is something that traditional epidemiological data could never pick up," Gire noted. "It really demonstrates the power that deep sequencing can have in an outbreak situation."

News, Ebola, Kahn, August 26 2014 One Third

Sheik Humarr Khan | Pardis C. Sabeti

The samples the team analyzed reveal that the 2014 virus genome is changing at a rapid rate, and its unique mutations may be influencing the 2014 outbreak's severity, the researchers say.

Tragically, five co-authors who contributed greatly to research efforts in Sierra Leone — Mohamed Fullah, Mbalu Fonnie, Alex Moigboi, S. Humarr Khan, and Alice Kovoma — contracted Ebola virus and passed away before publication of the sequencing study.

"I personally worked very closely with both Drs. Khan and Fullah," Gire said, "and so their deaths hit particularly hard for me. Dr. Khan was truly an inspirational figure, with a clear vision for the clinic at Kenema Government Hospital, and for Sierra Leone. Mohamed Fullah was also an exceptional man, and he was highly regarded by the community. Everyone always referred to him as the only man in Kenema that could actually diagnose malaria."

The deaths of these individuals underscore the need to work diligently to understand the evolution and trajectory of the current Ebola outbreak. As of 22 August, the World Health Organization has reported 2,615 suspected and confirmed cases of the disease, with 1,528 confirmed deaths from the virus.