Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study
Sissoko, Daouda
Duraffour, Sophie
Kerber, Romy
Kolie, Jacques Seraphin
Habib Beavogui, Abdoul
Camara, Alseny Modet
Colin Pharm, Géraldine
Rieger, Toni
Oestereich, Lisa
Pályi, Bernadett
Wurr, Stephanie
Guedj, Jeremie
Tram Nguyen, Thi Huyen
Eggo, Rosalind M.
Watson, Conall H.
Edmunds, John
Akoi Bore, Joseph
Raymond Koundouno, Fara
Cabeza-Cabrerizo, Mar
Carter, Lisa L.
Kafetzopoulou, Liana Eleni
Kuisma, Eeva
Michel, Janine
Patrono, Livia V.
Rickett, Natasha Y.
Singethan, Katrin
Rudolf, Martin
Lander, Angelika
Pallasch, Elisa
Bockholt, Sabrina
Rodríguez, Estefanía
Di Caro, Antonino
Wölfel, Roman
Gabriel, Martin
Gurry, Céline
Formenty, Pierre
Keïta, Sakoba
Malvy, Denis
Carroll, Miles
Anglaret, Xavier
Günther, Stephan
Background
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.
Methods
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.
Findings
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.
Interpretation
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.
Funding
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.