Recent development on sexual transmission of Ebola virus

Two studies published on 14 October 2015 in the New England Journal of Medicine provide insights into sexual transmission of Ebola virus and the duration of virus persistence in semen. The first study by Mate et al provides evidence of sexual transmission from a convalescent male survivor to his partner 179 days after the onset of disease, and 155 days after the clearance of Ebola virus from his blood. The second study by Deen et al summarises the results of a longitudinal monitoring of Ebola virus genetic material (RNA) in semen among survivors, demonstrating the presence of viral RNA in semen up to nine month after disease recovery.

The study from Mate et al. reports about the epidemiological and molecular investigations around a suspicion of late sexual transmission of Ebola virus disease (EVD) in Liberia [1]. In March 2015, a 44-year-old woman was confirmed to be infected by EVD:

• Investigations did not identify any link to an acute EVD patient thus raising the possibility of a potential sexual transmission by recent unprotected vaginal intercourse with a male Liberian EVD survivor, who had onset of EVD 6 months before, in September 2014. This survivor was discharged early October 2014 after clinical recovery and two consecutive blood samples tested negative for Ebola virus (EBOV) using a  molecular assay.
• In the aftermath of the occurrence of EVD in his partner, EBOV RNA was identified in his semen on 27 March 2015. Two successive semen samples were negative one month later. Blood samples were negative and virus culture on semen samples was unsuccessful.
• Additional molecular analyses discarded the possibility of other EVD transmission routes for the reason that the virus was phylogenetically not closely linked with the last cluster of EVD cases identified in early 2015. Further, EBOV genomes from the patient and the survivor were almost identical, differing in only one nucleotide position.
• This molecular finding and epidemiological investigation gives evidence of a direct sexual transmission of EBOV through unprotected vaginal intercourse.

The study by Deen et al summarises preliminary findings of a pilot  study focusing on the detection of RNA by quantitative RT-PCR in semen involving 100 male EVD survivors in Sierra Leone [2]. The proportions of men with positive EBOV RNA semen samples decreased over time from 100% (9/9) at two to three month after onset of symptoms, to 65% (26/40) at four to six months and to 26% (11/43) at seven to nine months after the onset. The shortest time after EVD onset that an initial semen specimen was negative was 4 months (128 days). The longest time after EVD onset that the semen was found positive was 9 months (284 days). Follow-up of this cohort is ongoing with virus-isolation assays performed to better assess the semen infectivity.

ECDC comment

Both studies report important findings on the sexual transmission of EVD and the potential persistence of the virus in semen. They need to be taken into account during the follow-up of the EVD survivors [3]. Sexual transmission of EVD is a rare event and has not been the main mode of transmission during the current EVD outbreak in West Africa. However, sexual transmission can lead to the occurrence of rare and sporadic EVD cases. It is often challenging to disentangle the exact route of transmission of such sporadic cases which requires an in-depth investigation as shown by Mate et al [1]. Importantly, the study of Mate et al showed that sexual transmission of EVD can occur up to 6-month after disease recovery. This finding is of public health importance and stresses the need to maintain enhanced surveillance for EVD to control the outbreak and achieve a resilient zero case during the Ebola response phase 3 and to strictly apply WHO interim recommendations with regards to sexual transmission [4, 5].

The study by Deen et al provides molecular insights into the clearance of viral RNA in semen up to nine months after onset of symptoms [2] . However, the assay used can detect either intact replicating virus or smaller RNA fragments, unable to replicate and infect a host cell. It is not possible yet to assess the prevalence of viable and transmissible virus in semen as viral culture is on-going. Systematic surveys of survivors are still needed to better assess the possible persistence of EBOV in semen and other immunologically privileged sites such as  eye, amniotic fluid, placenta, breast milk and the central nervous system as reported by WHO [6].Based on this findings, the evidence of sexual transmission up to six months after recovery from an EVD survivor to his or her partner, and the late detection of viral RNA emphasise the need to strictly apply WHO interim recommendations with regards to sexual transmission [5].

References 

1. Mate, S.E., et al., Molecular Evidence of Sexual Transmission of Ebola Virus. New England Journal of Medicine. 0(0): p. null.
2. Deen, G.F., et al., Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors — Preliminary Report. New England Journal of Medicine. 0(0): p. null.
3. Sprecher, A., Handle Survivors with Care. New England Journal of Medicine. 0(0): p. null.
4. World Health Organization. Ebola response phase 3: Framework for achieving and sustaining a resilient zero. [Internet] 2015  [cited 2015 Oct 16]; 
5. World Health Organization. Ebola virus disease - Fact sheet No103. [Internet] 2015; 
6. World Health Organization. Persistent virus in people recovering from Ebola virus disease. [Internet] 2015  [cited 2015 Oct 15];