Abstract
By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking.
Highlights
The Ebola virus disease (EVD) outbreak in west Africa lasted more than 2 years, affected almost 29 000 people in Guinea, Liberia, and Sierra Leone, and resulted in more than 11 000 deaths
On Jan 14, 2016, WHO declared the end of the EVD outbreak in Liberia, with all known chains of transmission stopped in west Africa
The longest time after the onset that a semen specimen tested positive was 101 and 82 days by RT-PCR and virus isolation, respectively. While these studies provided proof-of-concept for filovirus persistence in seminal fluid, we designed a larger longitudinal study to quantitatively describe the dynamics of Ebola virus RNA load in seminal fluid and estimate the parameters of the clearance kinetic using mathematical modelling
Summary
The Ebola virus disease (EVD) outbreak in west Africa lasted more than 2 years, affected almost 29 000 people in Guinea, Liberia, and Sierra Leone, and resulted in more than 11 000 deaths. On Jan 14, 2016, WHO declared the end of the EVD outbreak in Liberia, with all known chains of transmission stopped in west Africa. there is concern about persistence of the Ebola virus in survivors, in the male reproductive tract. In conjunction with the discovery of filoviruses in 1967 in Marburg, Germany, Marburg virus has been shown to be sexually transmitted by men who shed the virus in seminal fluid after recovery from the disease. Reports from EVD patients subsequently confirmed virus persistence in seminal fluid after recovery for Ebola and Sudan viruses. A cross-sectional study detected Ebola virus RNA in seminal fluid of EVD survivors of the 2014–16 epidemic up to 9 months after disease onset. The Ebola virus disease (EVD) outbreak in west Africa lasted more than 2 years, affected almost 29 000 people in Guinea, Liberia, and Sierra Leone, and resulted in more than 11 000 deaths.. There is concern about persistence of the Ebola virus in survivors, in the male reproductive tract.. In conjunction with the discovery of filoviruses in 1967 in Marburg, Germany, Marburg virus has been shown to be sexually transmitted by men who shed the virus in seminal fluid after recovery from the disease.. Reports from EVD patients subsequently confirmed virus persistence in seminal fluid after recovery for Ebola and Sudan viruses.. A cross-sectional study detected Ebola virus RNA in seminal fluid of EVD survivors of the 2014–16 epidemic up to 9 months after disease onset. There are no quantitative virus-load data for seminal fluid to facilitate mathematical modelling of virus clearance
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