REVIEW URRENT C OPINION

Ebola virus as a sexually transmitted infection Karen E. Rogstad a and Anne Tunbridge b

Purpose of review The ongoing Ebola virus epidemic in West Africa is a major global health challenge. The main mode of transmission is through contact with bodily fluids and skin of those infected or who have died. This review was undertaken to consider the evidence for transmission by contact with bodily fluids occurring through sexual activity. Recent findings No cases in the previous 20 outbreaks or the current outbreak in West Africa have been shown to be sexually transmitted, although other types of viral haemorrhagic fever have had sexual transmission implicated. Ebola virus is found in sites and fluids associated with sexual activity but this occurs at different stages of the disease. Persistence in the convalescent period occurs in rectum, vagina and semen, with persistence in semen being longest of up to at least 101 days. Recommendations based on this data are that those recovering from Ebola virus disease should abstain from all sexual intercourse, or if this is not possible, use condoms, for 3 months after the onset of symptoms. Summary There is theoretical plausibility for sexual transmission of Ebola virus but there has been no evidence of this occurring. Further research is needed to consider if sexual activity contributes to the epidemic in order to inform individuals with regard to avoiding acquisition or transmission by those recovering from Ebola virus disease. Keywords condoms, Ebola, Ebola virus disease, Marburg virus, semen, sexually transmitted infection, travel, viral haemorrhagic fever

INTRODUCTION The Ebola virus outbreak in West Africa is a major challenge to global health and devastating for individuals and communities affected by Ebola virus disease (EVD). It is larger than the other 20 outbreaks and by the end of November 2014 more than 20 000 confirmed and probable cases were predicted, with an estimated fatality rate of 70.8% [1 ]. Even if vaccine trials prove effective, there will be a significant delay in widespread vaccination to control the epidemic, and it is likely there will be an ongoing endemic in West Africa and potential expansion of the epidemic for some time to come [1 ]. Advice is required for individuals to avoid acquiring or, if infected, transmitting the virus. From a public health view modelling is being used and may assist in advising on interventions and predict the future course of the epidemic [2 ]. Transmission is considered mainly to be caused by direct contact with the blood, body fluids, or skin of patients, or those who have died from EVD [3]. Does sexual transmission therefore have a role? &

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PLAUSIBILITY FOR SEXUAL TRANSMISSION The majority of patients, 60.8%, infected by Ebola are young adults (aged 15–44 years), whereas they represent only 44% of the population [1 ]. Sexually transmitted infections (STIs) also predominantly affect this age group, although peak incidence for STIs is 15–24 years [4]. Some of the major risk factors for Ebola virus transmission are to carers, through direct contact, while nursing those infected [5]; or &

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HIV and Sexual Health, Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine and bInfectious Diseases, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Infectious Diseases and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, UK Correspondence to Karen E. Rogstad, HIV and Sexual Health Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK. Tel: +44 114 271 1900; e-mail: [email protected] Curr Opin Infect Dis 2015, 28:83–85 DOI:10.1097/QCO.0000000000000135

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Sexually transmitted diseases

given to the role in sexual transmission of those who are infected but remain asymptomatic [14].

KEY POINTS  There have been no definite cases identified of the sexual transmission of Ebola virus.  The closely related Marburg virus, which also causes viral haemorrhagic fever, has been sexually transmitted.  Transmission through oral contact may be more likely in the early phase of infection as levels of virus in saliva rise early in the course of disease.  Ebola virus persists in semen for up to 3 months and may do so for longer.  It is recommended that because of the potential for sexual transmission those who have recovered from Ebola infection should abstain from sexual intercourse, including oral, for 3 months, or if this is not possible, use a condom.

those handling bodies of the deceased [6], in whom viral loads are the highest; or inadequately protected healthcare workers. At the end of October 2014, 521 personnel had been infected, of whom 272 have died [7 ]. If sexual transmission does occur, it is unlikely to be a major contributor, and those with symptoms will, in the most part, be too ill for sexual intercourse. Sexual contact could potentially occur through the close skin to skin contact involved in sexual intercourse. Additionally sexual intercourse also includes direct contact with bodily secretions such as vaginal secretions, semen, saliva through kissing and oral sex, and faecal products in anal sex. There is clear evidence from previous epidemics of the presence and persistence of Ebola virus in these samples and sites [8–12]. In the acute phase, PCR for Ebola was present in eight of 12 (67%) of saliva samples, and 50% of stool/faeces samples [9]. In one convalescent-only study [10], Ebola virus was no longer found in saliva, but was detected in vaginal, rectal and seminal fluid. A study of 28 patients recovering from Ebola found only semen samples remained positive in samples taken between 12 and 157 days [11]: the virus was detected in six of the eight semen samples, but only by PCR and not by culture or antigen detection method. One study found infectious virus in the seminal fluid of one patient at day 82 [5]. A Centers for Disease Control and Prevention review combining studies [13 ] to determine the length for which RNA was detected after symptom onset, found it to be 6 days on skin, 8 days in saliva, 29 in stool/faeces, 33 days in vaginal fluid and 101 days in semen. Consideration may also have to be

EVIDENCE FOR SEXUAL TRANSMISSION Despite good theoretical reasons to consider that sexual transmission may be relevant, there appear to be no documented cases in the published literature for Ebola. For other viral haemorrhagic fevers there is some evidence of sexual transmission. Marburg virus has been sexually transmitted [15] and a case of potential sexual transmission of Crimean–Congo haemorrhagic fever (CCHF) [16 ] has been described in Turkey. In another case CCHF caused an epididymo-orchitis [17]; the author suggested this implied sexual transmission could be possible (epididymitis is a recognized complication of the sexually transmitted infections Neisseria gonorrhoeae and Chlamydia trachomatis). Because of the potential risk, despite no confirmed cases, the Centers for Disease Control and Prevention advise survivors of EVD to abstain from sexual intercourse including oral, or if this is not possible, to use condoms for up to 3 months after onset of disease [13 ]. &

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CONCLUSION At the present time despite biological plausibility for the sexual transmission of Ebola virus, there is no evidence of this occurring. However, because of the persistence of viral RNA in semen, vaginal and rectal samples, healthcare professionals caring for victims should ensure that advice is given on discharge, and public health messages given for those being cared for outside hospital settings. It is essential that further research is performed in this area to enable evidence-based advice to be given, both for those living within affected areas as well as those travelling to or from these areas who may be sexually active, as sexual intercourse and unprotected sexual intercourse is associated with travel [18,19]. Additionally, if sexual transmission is found to be a significant risk, this would need to be included in modelling of the epidemic. Genomic surveillance, as used to elucidate viral origin and transmission thus far [20 ], is likely to assist in determining if sexual transmission is relevant and its role. &

Acknowledgements None. Financial support and sponsorship None. Volume 28  Number 1  February 2015

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Sexual transmission of Ebola virus Rogstad and Tunbridge

Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. WHO Ebola response team. Ebola virus disease in West Africa: the first & 9 months of the epidemic and forward projections. New Engl J Med 2014; 371:1481–1495. This review summarizes the 2014 West African Ebola outbreak and considers demographic data and mortality rates and explores the issues which lead them to predict an endemic for the medium term. 2. Lewnard JA, Mbah MLN, Alfaro-Murillo JA, et al. Dynamics and control of & Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysis. Lancet Infectious Diseases 2014; 14:1189–1195. Mathematical modelling is used to predict how various interventions can be used to avert cases of EVD and death, and thus inform planning. 3. Dowell SF, Mukunu R, Ksiazek TG, et al. Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 1999; 179 (Suppl 1):S87–S91. 4. Fenton K, Rogstad KE. Sexually transmitted infections: why are they important? In: ABC of Sexually Transmitted Infections, 6th edition. Oxford: Wiley Blackwell. pp. 1-10. 5. Khan AS, Tshioko FK, Heymann DL, et al. The re-emergence of Ebola haemorhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidemies a Kikwit. J Infect Dis 1999; 179 (Suppl 1):S28– S35. 6. Hewlett BS, Amola RP. Cultural contexts of ebola in Northern Uganda. Emerg Infect Dis 2003 9:1242. http://wwwnc.cdc.gov/eid/article/9/10/02-0493. DOI: 10.3201/eid0910.020493. [Accessed December 2014]. 7. World Health Organisation. Ebola response roadmap situation report. & http://apps.who.int/iris/bitstream/10665/137376/1/roadmapsitrep_29Oct2014_eng.pdf?ua¼1 [Accessed 2 December 2014]. Data on healthcare workers and mortalities from EBV in the 2014 epidemic.

8. Bausch DG, Towner JS, Dowell SF, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis 2007; 196 (Suppl 2):S142–S147. 9. Towner JS, Rollin PE, Bausch DG, et al. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol 2004; 78:4330 – 4341. 10. Rodriguez LL, De Roo A, Guimard Y, et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 1999; 179 (Suppl 1):S170–S176. 11. Rowe AK, Bertolli J, Khan AS, et al. Clinical, virologic, and immunologic followup of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. J Infect Dis 1999; 179 (Suppl 1):S28–S35. 12. Richards GA, Murphy S, Jobson R, et al. Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects. Crit Care Med 2000; 28:240 – 244. 13. Centers for Disease Control and Prevention. Review of Human-to-Human && Transmission of Ebola Virus. http://www.cdc.gov/vhf/ebola/transmission/human-transmission.html. [Accessed 2 December 2014]. This review summarizes the data on virus detection in bodily fluids and persistence in the convalescent phase, providing the rationale for advice on abstinence from sexual intercourse for 3 months. 14. Leroy EM, Baize S, Volchkov VE, et al. Human asymptomatic Ebola infection and strong inflammatory response. Lancet 2000; 355:2210–2215. 15. Martini GA, Schmidt HA. [Spermatogenic transmission of the ‘Marburg virus’. (Causes of ‘Marburg simian disease’)]. Klin Wochenschr 1968; 46:398–400. 16. Ergonul O, Battal I. Potential sexual transmission of Crimean-Congo hemor& rhagic fever infection. Jpn J Infect Dis 2014; 67:137–138. This single case study describes the first documented case of potential sexual transmission of CCHF. 17. Aksoy HZ, Yilmaz G, Aksoy F, Koksal IJ. Crimean-Congo haemorrhagic fever presenting as epididymo-orchitis. Clin Virol 2010; 48:282–284. 18. Rogstad KE. Sex, sun, sea, and STIs: sexually transmitted infections acquired on holiday. BMJ 2004; 329:214–217. 19. Vivacnos R, Abubakar I, Hunter PR. Foreign travel, casual sex & STIs: systematic review and meta-analysis. Int J Infect Dis 2010; 14:e842–e851. 20. Gire SK, Goba A, Andersen KG, et al. Genomic surveillance elucidates Ebola & virus origin and transmission during the 2014 outbreak. Science 2014; 345:1369–1372. This review describes using genomic surveillance to identify viral origin and transmission links.

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Ebola virus as a sexually transmitted infection.

The ongoing Ebola virus epidemic in West Africa is a major global health challenge. The main mode of transmission is through contact with bodily fluid...
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