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Rapid, local sequencing of Ebola genomes reveals sources of disease flare-ups
Generating Ebola virus genome sequences in a tent-based facility in Sierra Leone helped researchers determine unconventional origins of new infections in the country, underscoring the importance of local sequencing in controlling disease flare-ups, according to recent findings.
Through rapid and local sequencing, the research team, led by the University of Cambridge and Wellcome Trust Sanger Institute, found that new infections occurring toward the end of the Ebola epidemic were transmitted through alternative routes, including semen and breast milk.
Jeremy Farrar
“Close contact with an infected individual is still by far the most common way for Ebola to spread, but this study supports previous research suggesting that the virus can persist in bodily fluids for a long time after recovery,” Jeremy Farrar, PhD, director of the Wellcome Trust, said in a press release. “These unusual modes of transmission may have contributed to isolated flare-ups of infections toward the end of the epidemic.”
The researchers investigated new infections in a temporary genome-sequencing facility based in an air-conditioned tent in Makeni, Sierra Leone. The facility, which began operations in April 2015, was able to provide local sequencing capability without the need for sample shipment.
“During the initial part of the Ebola epidemic, several teams were sequencing samples, but the delays caused by shipping the samples out of West Africa made it difficult to use the sequence data for investigating new chains of transmission,” Ian Goodfellow, PhD, head of the virology division at the University of Cambridge, said in the release. “Often by the time the data were published, the samples were 6 months old. To be able to rapidly identify the source of new cases, we need to sequence samples and release data in real-time, share samples and share data as they are produced.”
During their investigation, Goodfellow and colleagues produced 554 complete Ebola virus genome sequences from 855 blood, buccal swabs, semen and breast milk samples collected in Sierra Leone between December 2014 and September 2015. The samples were combined with 1,019 additional samples sequenced by other research groups in order to gain more insight into the viral variants circulating in the country.
An evolutionary analysis revealed there were at least nine viral lineages circulating in Sierra Leone. Eight lineages derived from a single variant that emerged in the country in June 2014, and the remaining viruses were introduced through a separate lineage from Guinea.
By June 2015, only three viral lineages were detected in new cases. With support from the Sierra Leone Ministry of Health, WHO, and the CDC, researchers at the local sequencing facility were able to help field workers trace the source of new infections. They discovered that a small cluster of new infections in Tonkolili, which had been Ebola-free for 130 days, was caused by a patient infected with Ebola while traveling to a district with active transmission. With this information, the investigators were able to determine the previously circulating strain was not re-emerging in the area. They also found that another small flare-up in the country originated from a woman who may have transmitted Ebola to her baby through breast milk. The woman had no symptoms, and serum samples were negative for Ebola; however, the virus was detected in her breast milk. In addition, genome-sequencing analyses revealed that a woman who died 50 days after the last reported case in the region contracted Ebola virus from a male survivor she had sexual contact with, suggesting the virus was transmitted sexually.
In a separate study conducted by Mamadou S. Sow, MD, of the infectious diseases department at Donka University National Hospital, Guinea, and colleagues, the researchers found evidence supporting Ebola virus RNA may persist in the semen of some male survivors for as long as 9 months. However, they were unable to confirm the duration of semen infectivity and recommended that health officials continue to promote safe sex practices among Ebola survivors to reduce the risk for flare-ups.
Based on their findings, Goodfellow and colleagues concluded that sequencing and data sharing in the midst of infectious disease outbreaks, and rapid and local sequencing at the end of an outbreak, can help control future outbreaks.
“With the increasing global risk of viral zoonosis, the success of this project provides a strong incentive to establish and maintain local sequencing facilities throughout the world,” they wrote. – by Stephanie Viguers
Reference:
Sow MS, et al. J Infect Dis. 2016;doi:10.1093/infdis/jiw078.
Disclosures: The researchers report no relevant financial disclosures.