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Dynamics of Ebola Virus Clearance in Semen in Guinea
Daouda Sissoko1; Sophie Duraffour2; Jacques Kolie3; Abdoul H. Beavogui4; Thi Huyen Tram Nguyen5; Jeremie Guedj6; Denis Malvy7; Miles W. Carroll8; Xavier Anglaret9; Stephan Gunther10
1INSERM U897, Bordeaux, France;2Bernhard-Nocht Inst for Tropical Medicine, Hamburg, Germany;3Ministry of Hlth Guinea, Conakry, Guinea;4Cntr de Recherche en Santé Rurale de Mafèrinyah, Conakry, Guinea;5UMR 1137, INSERM, Université Paris Diderot, Paris, France;6French National Inst of Hlth and Med Rsr, Paris, France;7CHU de Bordeaux, Bordeaux, France;8Public Hlth England, Salisbury, United Kingdom;9INSERM, Abidjan, Côte d'Ivoire (Ivory Coast);10European Mobile Laboratory Project, Hamburg, Germany
While it is well known that testes may be a reservoir for long term persistence of Ebola virus (EBOV), the dynamics of the persistence of EBOV in semen remained unexplored. We aimed to estimate the probability of EBOV RNA clearance in semen over time.
We enrolled a cohort of 25 men discharged from three Ebola Treatment Units (ETU) in Coastal region of Guinea between February 6, 2015 and July 6, 2015. Semen specimens were obtained every 3-6 weeks until reaching non-detectable levels of EBOV RNA (eg, CT values ≥ 45) on two consecutive samples. Specimens were tested on-site using Altona RT-PCR. Furthermore, a nonlinear mixed effect model was used to estimate the slope of evolution of Ct values over time
A total of 116 semen samples were collected. The median time between EVD onset and first semen collection was 49 days (IQR: 40-85). The median time between first and last semen collection was 193 days (IQR: 150-204). Of the 25 participants, 18 (72%) had a positive EBOV RT-PCR in the first semen sample. The median Ct value in the 18 positive semen was 28.1 (IQR= 22.4-36.3). The semen of the patient having the longest follow-up was still positive to EBOV at day 300 post-disease onset.
Using a linear mixed model, the mean increase of Ct in semen was estimated to +0.086 per day (SD 0.65), corresponding to a mean decrease of RNA of -0.87 log10 copies/ml per month. Based on these numbers, the time to achieve negative RT-PCR in semen in 50% and 90% of the patients was predicted at 127 (95% Prediction interval -95% PI-= 71-221) and 375 (95% PI=222- 638) days, respectively (Figure 1).
About 10% of patients may have detectable viremia in semen up a year after onset of disease. Therefore long term programs of care for EVD survivors should include implementation of semen testing, dedicated counselling and condom use in order to avoid potential sexual transmission. The evaluation of drug intervention among individuals harbouring EBOV insemen is highly desirable.