January 29, 2018
Early in the Zika virus epidemic in the Americas, evidence confirmed reports suggesting that this mosquito-borne virus could also be transmitted sexually. The majority of reports concerned transmission from male to female sexual partners. The simultaneous increase in public awareness of detrimental neonatal outcomes of mothers who were infected with Zika virus during pregnancy, sparked concerns over this mode of transmission. At the Institute of Tropical Medicine in Antwerp, Belgium, our aim is to contribute to the knowledge base of non-vector transmission.
We initiated prospective research to study the frequency and replication fitness of Zika virus in the semen of Zika infected patients. To monitor the kinetics of Zika viral loads over time 1 2, our first study population consisted of symptomatic travelers who had returned to non-endemic areas. Using reverse-transcription polymerase chain reaction (RT-PCR), we detected Zika virus RNA in the semen of 60% of participants. The median duration of viral shedding in semen was 83 days, the longest duration was 144 days after symptom onset. We also studied Zika virus persistence in semen from men living in Trinidad and Tobago in 2016. 39% of infected men in this area with vector-borne transmission had Zika virus in semen. The duration of viral shedding was of similar length.
Interestingly, participants with confirmed Zika virus infection had semen abnormalities such as leukospermia, haematospermia or oligospermia, irrespective of Zika virus detection in semen. This finding suggests, in line with animal studies, that Zika virus infection leads to structural damage to the male reproductive organs. As demonstrated by the detection of Zika virus RNA in the seminal fluid of men who had had successful vasectomy, the presence of spermatocytes is not required for prolonged shedding of Zika virus from the male reproductive organs. However, the actual histological sites of viral gonadotropism and persistence remain to be discovered.
To date, isolation of Zika virus from semen is commonly regarded as an indication of infectivity. In our studies, isolation of virus was only successful in some samples with high viral load, collected within 3 weeks of symptom onset. Although this timeframe roughly correlates with the maximum duration of sexual transmission hitherto reported, we are hesitant to rule out the potential for sexual transmission as long as Zika virus is detected by RT-PCR.
Elaborating on our findings, we are currently looking into other methods to determine the replication fitness of Zika virus in semen. We are studying the correlation between successful virus isolations and the detection of Zika virus peptides in the same semen sample, using a prototype NS1-antigen test 3. Another strategy that we are exploring is an RT-PCR assay to detect ‘negative strand RNA’ of Zika virus, the presence of which is only anticipated when Zika virus is actively replicating.
In spite of recent progress, many unknowns remain regarding the sexual transmission of Zika virus. In March 2017, we participated in the WHO Sexual Transmission of Zika virus Expert Meeting in Geneva to identify the knowledge gaps and research methods to address them. A recent comment summarized the current status, challenges and research priorities 4 5. A multidisciplinary approach and joint efforts by the international scientific community, such as facilitated by the ZikaPLAN consortium, is certain to bear more fruit.
Ralph Huits MD, infectious disease physician, Dept. of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
Lieselotte Cnops PhD, molecular biologist, Dept. of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
1 Huits RM, De Smet B, Ariën KK, Van Esbroeck M, de Jong BC, Bottieau E, Cnops L. Kinetics of Zika virus persistence in semen. Bull World Health Organ. 2016; doi:10.2471/BLT.16.181370
2 Huits R, De Smet B, Ariën KK, Van Esbroeck M, Bottieau E, Cnops L. Zika virus in semen: a prospective cohort study of symptomatic travellers returning to Belgium. Bull World Health Organ. 2017;95: 802–809. doi:10.2471/BLT.17.181370
3 Cnops L, Nakayama EE, Caron E, Eggermont K, Van Esbroeck M,Bottieau E, Jacobs J, Shioda T and Huits R. Detection of zika virus NS1 antigen in semen by a prototype rapid test. Abstracts 10th ECTMIH. Oral Presentation Sessions. Trop Med Int Heal. 2017;22: p 27. doi:10.1111/tmi.12978
4 Kim CR, Counotte M, Bernstein K, Deal C, Mayaud P, Low N, et al. Investigating the sexual transmission of Zika virus. Lancet Glob Heal. The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 3.0 IGO license; 2018;6: e24–e25. doi:10.1016/S2214-109X(17)30419-9
5 Sexual transmission of ZIKV meeting of experts. Sexual transmission of Zika Virus : Current status , challenges and research priorities. 2017; 1–18. Available: http://www.who.int/reproductivehealth/zika/sexual-transmission-experts-meeting/en/