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Scientists trace Ebola’s genetic path in Africa, weighing role of mutations

Scientists are using blood samples collected throughout the Ebola outbreak to map the virus’ spread from country to country by tracking tiny mutations in its gene sequences.

The picture is not yet complete, but intriguing discoveries have been made. Virus mutations first detected in Sierra Leone last spring were found later in Liberia and Mali, and scientists are examining whether this resulted from the chance movements of people across borders.

While some scientists think it is unlikely that the mutations made a difference in how the virus functioned, others are looking at whether this version of the virus had properties that made it more capable of causing infection.

Scientists look for viral mutations because of their potential influence on the effectiveness of diagnostics or treatments. Researchers have changed Ebola diagnostic tests and experimental treatments based on information about how the virus has evolved from previous outbreaks to the one in West Africa.

Genetic mutations are also beginning to serve as a tool to understand the overall course of the epidemic, which could offer insights into how to improve the response to outbreaks.

“They let us trace history,” said Daniel J. Park, group leader of viral computational genomics at the Broad Institute of MIT and Harvard.

Tracking changes in the virus’ genetic sequence is an objective endeavor, unlike interviewing people on the ground.

“We can tell you with a high likelihood that this sequence is derived from this other sequence,” said Jeffrey R. Kugelman, the chief of the bioinformatics branch of the Center for Genomic Sciences at the Army Medical Research Institute of Infectious Diseases.

But epidemiologists’ interviews rely heavily “on the quality of your conversations with people, and whether they’re telling the truth and whether they understood the situation properly,” he said.

Still, making sense of the scientific evidence from sequencing relies on good records about where and when samples were taken. Both strategies are needed to tell a full story, said Edward C. Holmes, a fellow at the University of Sydney in Australia.

Sequences of viruses from only about 250 people were made publicly available during the first year of the outbreak in West Africa, which is thought to have infected 25,000.

Scientists have assigned the sequences to three clusters plus the original versions of the virus discovered in Guinea in March 2014. The three clusters are slightly mutated descendants of the Guinean viruses, and they were found circulating in Sierra Leone two to three months later.

One of the most intriguing findings so far is that viral descendants of what is known as cluster two have been found in the blood samples of all Liberian Ebola patients whose viruses have been sequenced and made public, and in patients in Mali who had traveled from and lived in Guinea.

Based on scientific publications, documents and interviews with people in Sierra Leone, cluster two was first detected in blood drawn May 23 from Victoria Yillia, one of the country’s first confirmed Ebola patients.

According to interviews with Yillia, who survived, and her relatives and neighbors in eastern Sierra Leone, people with symptoms of Ebola had already been dying for well over two months, as the outbreak went unrecognized by the authorities. Some of them crossed over to Liberia and Guinea, they said.

Sierra Leone’s silent epidemic of illness and death can be traced back to late February 2014 with the sickness of a woman named Sia Wanda Koniono. She became ill in the Kailahun district when she returned to the country after traveling in Guinea, according to people close to her. Koniono crossed back to Guinea for medical treatment and died there. Others exposed to her there were later confirmed to have Ebola, said Dr. Michel Van Herp of Doctors Without Borders.

A report by officers working for the World Health Organization and Guinea, which has not been made public, shows that officials there knew in March about Koniono’s death from hemorrhagic fever and the illness of her daughter. However, no one followed up on this information by tracing their contacts across the border in Sierra Leone, according to local officials.

Doctors Without Borders staff members said in interviews that they, too, had known about Koniono and that one worker had sent an email mentioning her to Dr. Sheik Humarr Khan, then the point person for viral hemorrhagic diseases in Kenema, Sierra Leone, in late March, and to a laboratory worker there in early April. But those emails were not answered and may never have been opened, the laboratory worker said, because Internet connections were intermittent. Khan later died of Ebola.

By sequencing more blood samples taken in Guinea at important times, scientists say it may be possible to determine whether Yillia’s version of the virus arose in Sierra Leone during the months when the virus was probably spreading there silently, and then reseeded in Liberia and Guinea, ultimately becoming a dominant version of the virus in those countries.

“This sort of dramatic change in the virus population could be explained by chance,” said Dr. Pardis Sabeti, a Harvard professor and computational biologist at the Broad Institute.

Still, she said, her laboratory and others are studying the function of the virus, trying to see whether the mutations might have made that version of the virus more capable of infecting people at the time the epidemic exploded.

“The genome of the virus is so small, and this outbreak so devastating,” Sabeti said, “as a scientific community, we should leave no stone unturned.”

A sequencing laboratory was recently set up in Liberia with support from the Army Medical Research Institute of Infectious Diseases because of delays in transporting Ebola samples across borders. In future outbreaks, sequencing at diagnostic laboratories in affected countries could “become an important tool for seeing what is going on as it happens,” said Andrew Rambaut of the Institute of Evolutionary Biology at the University of Edinburgh. But, he said, “it will need an expectation that data will be shared immediately.”

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