The release of two new studies today sheds new light on the threat of sexual transmission of Ebola by survivors, one hinting that the virus can persist in semen for as long as 9 months, and the other providing strong genetic evidence of sexual transmission.
Both studies appear in the latest online edition of the New England Journal of Medicine (NEJM) and come at a time when medical issues in Ebola survivors are making headlines in the wake of a Scottish nurse who is now critically ill with Ebola complications after her initial hospital discharge in January.
Survivors can harbor the virus in immune-protected areas, such as the eyes and testes, but researchers haven’t yet pinpointed for how long. Efforts are well under way in the outbreak region and elsewhere to assess the risks, including today’s findings.
Though sexual Ebola transmission is thought to be rare, the risk has health implications for not only survivors and their contacts, but also for the control of the virus in outbreak regions. Of about 17,000 Ebola survivors in West Africa’s outbreak, more than 8,000 are male.
RNA drop-off over time in semen
In the first study, researchers from Sierra Leone and their collaborators reported preliminary results from studying the semen of male survivors who were at different points in their recovery in that country. The team used reverse-transcriptase polymerase chain reaction (RT-PCR) testing to detect Ebola viral RNA in semen samples. The research team included scientists from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC).
Semen samples were provided by 93 men from Freetown who were between 2 and 10 months past their onset of Ebola illness. The men were among a convenience sample of 100 male survivors.
All nine of the men who were tested within 3 months of their first symptoms tested positive for genetic evidence of Ebola. Of those tested between the 4- and 6-month mark, 26 (65%) tested positive. Among 43 men whose semen was tested 7 to 9 month after they first got sick, 11 (26%) tested positive.
Amara Jambai, MD, MSc, chief medical officer for Sierra Leone’s Ministry of Health and Sanitation, said in a CDC press release that part of the country’s goal of getting to zero cases and caring for survivors includes understanding how the disease affects their recovery. “Survivors are to be commended for contributing to the studies that help us understand how long the virus may persist in semen.”
The CDC said it’s still not clear why some participants cleared fragments of Ebola virus earlier than others, and the agency said it is doing more tests on the samples to see if the virus in the survivors’ semen is live and possibly infectious.
Tom Frieden, MD, MPH, CDC director, said in the statement that Ebola survivors face an increasing number of recognized health complications. “This study provides important new information about the persistence of Ebola virus in semen and helps us make recommendations to survivors and their loved ones to help them stay healthy.”
The CDC said male survivors in the three outbreak countries need appropriate education, counseling, and regular testing to gauge Ebola persistence in their semen. According to WHO guidance, until a male’s semen has tested negative twice, he is advised to abstain from all types of sex or use condoms. Hand washing is also recommended after physical contact with semen.
Strong case for sexual transmission
A second NEJM study describes the epidemiologic and genetic evidence that ties an infection in a 44-year-old Liberian woman who died in late March to sexual transmission from a survivor.
Her illness occurred after the country had been free of the virus for 30 days. An earlier investigation published in Morbidity and Mortality Weekly Report (MMWR) in May showed possible links, but the new study provides a detailed look at a full array of genetic sequences of the man’s blood and semen, blood of his sick contacts, and blood from the woman who died.
The case is also notable because the man’s semen showed evidence of Ebola RNA 199 days after his illness onset, or almost 7 months, much longer than previously thought. Until the man’s test results were known, viral RNA had been detected in semen up to 101 days after symptom onset, which is about 3.4 months.
Researchers found a strong genetic match between the virus found in the woman, in the male survivor, and in the man’s brother, connecting them to a known transmission chain from September 2014. Contact tracing didn’t turn up any other connections between the woman and other confirmed Ebola cases.
The team also found that genomes assembled from the survivor and the patient shared three substitutions that weren’t seen in 796 genomes from West Africa.
“Together, these data provide evidence of human-to-human [Ebola virus] transmission through sexual contact,” they wrote, though they included the caveat that they couldn’t rule out the possibility of transmission from sources that weren’t sampled.
Though much remains to be known about viral persistence in survivors’ semen, so far it appears that sexual transmission is relatively rare, the team said, adding that persistent infections and unprotected sex could lead to random disease flare-ups. They noted that although tests on the man’s semen sample weren’t able to detect live virus, the fact that they were able to assemble a nearly complete genome suggests that infectious particles may have been present.
Implications for outbreak response
In an editorial on both of the studies in the same issue of NEJM, Armand Sprecher, MD, MPH, with Doctors without Borders (MSF) in Brussels, said the Liberian sexual transmission study raises the question of how long male survivors can infect their sexual contacts, given evidence that the survivor passed the virus to the woman 6 months after recovery. He added that the preliminary results from the semen testing study starts the process of answering the question.
He wrote that the semen study’s findings should be considered preliminary until the next step of the investigation to look for infectious virus is complete. “However, no matter what they find, sexual transmission remains a rare event,” Sprecher said.
Though sexual transmission wouldn’t be the source of many new cases, it could spark late Ebola cases, which has implications for the outbreak response, he noted. Sexual transmission raises the possibility of people getting sick past 42-days, which is when the WHO typically declared the outbreak over in a given area.
Because of the possible late cases, the WHO recommends heightened surveillance for 90 days beyond the Ebola-free mark, though the Liberian sexual transmission study findings signal that the period should be extended.
Sprecher warned that labeling male survivors as an ongoing threat, however, might imperil the goal of treating them with compassion, due to the trauma they’ve endured from their own infections and from the illnesses and deaths of those around them. Poorly handled messaging about the risk might drive newly infected people into hiding, defeating surveillance efforts.
