Tracking the last Ebola cases in Sierra Leone

Ebola virus genomes were sequenced in a temporary laboratory at the outbreak treatment centre

David Goulding, Sanger Institute

Ebola virus

Some of the final cases of Ebola in Sierra Leone were transmitted via unconventional routes, such as semen and breastmilk, according to the largest analysis to date of the tail-end of the epidemic.

An international team of researchers has produced a detailed picture of the latter stages of the outbreak in Sierra Leone, using real-time sequencing of Ebola virus genomes carried out in a temporary laboratory in the country.

The research, published today (18th May) in the journal Virus Evolution, suggests that rapid sequencing of viral genomes in the midst of an epidemic could play a vital role in bringing future outbreaks under control, by allowing public health workers to quickly trace new cases back to their source.

Sierra Leone was the most widely affected of the three West African countries worst hit by the Ebola epidemic, with 14,124 cases and 3,956 deaths to date. Without effective vaccines or treatments for the infection, bringing the epidemic under control relied largely on public health measures such as the rapid identification and isolation of Ebola patients, contact tracing and quarantine, as well as encouraging safe burial practices.

By January 2015 cases in the three most-affected countries had started to decline, but isolated cases of the disease continued to flare up, even though all known transmission chains had been extinguished.

Researchers led by the University of Cambridge and the Wellcome Trust Sanger Institute began investigating these cases in a temporary genome sequencing facility set up by Professor Ian Goodfellow. Based in a tent at the Ebola Treatment Centre in Makeni, Sierra Leone, the facility provided in-country sequencing capability processing samples from patients in Makeni and surrounding areas in real time, without the need to be shipped out of the country.

The team generated 554 complete Ebola genome sequences from samples of blood, buccal swabs, semen and breast milk collected between December 2014 and September 2015 from Ebola isolation and treatments centres in the north and west of the country. These were combined with 1019 samples sequenced by other groups to create a picture of the viral variants present in Sierra Leone.

They found that during 2015 at least nine different lineages of the virus were circulating in Sierra Leone, eight of which evolved from a single variant that introduced Ebola to the country in June 2014. The remaining viruses came from a separate, geographically distinct lineage that originated in Guinea.

By linking a subset (21 samples) of the viral genomes with information about patients collected by fieldworkers, they identified the source of infection for some of the final Ebola cases in Sierra Leone, showing that some cases were acquired through unconventional transmission chains involving bodily fluids. This finding supports a growing body of evidence that the Ebola virus can be found in fluids such as semen or breast milk and may persist beyond the standard quarantine times.

“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. Often by the time the data was published the samples were six months old. To be able to rapidly identify the source of new cases we need to sequence and release data in real-time, share samples and share data as it’s produced.”

Senior author Prof Ian Goodfellow From the University of Cambridge

“During the epidemic combining our Ebola virus genome sequences with data from other groups gave us insight into how the virus was evolving and provided an important reference for tracking the source of new cases. The virus followed an expected pattern of evolution and didn’t acquire new mutations that would have made it more virulent or harder to detect, as some had feared. As the outbreak progressed, our data also show that quarantines, border control and checking methods were working, as movement of the virus within and between countries ceased.”

Dr Matt Cotten Joint senior author, from the Wellcome Trust Sanger Institute

The sequencing facility set up by the team has now been moved to the University of Makeni, where it forms the focal point of the new UniMak Infectious Disease Research Laboratory. The facility is providing world-class training to local scientists, which has proven crucial to sequencing the recent new cases of Ebola when no international staff were present.

“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. These unusual modes of transmission may have contributed to isolated flare-ups of infections towards the end of the epidemic.

“The success of this innovative project shows how important it is to carry out genome sequencing within the affected countries, and for the data to be shared in a rapid and open way as part of the epidemic response. Strengthening laboratory and surveillance facilities where they are currently lacking will also aid early detection, making the world better prepared for infectious disease outbreaks.”

Dr Jeremy Farrar Director of the Wellcome Trust

More information

Publication:

Armando et al. (2016) Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases. Virus Evolution; 18 May 2016; DOI: 10.1093/ve/vew016

Funding:

The research was funded by the Wellcome Trust and is a collaboration between the University of Cambridge and the Wellcome Trust Sanger Institute with support from the University of Edinburgh and Public Health England. The Ion Torrent sequencing machines were supplied by Thermo Fisher Scientific.