Zika virus is normally transmitted by mosquitos, but cases of sexual transmission have been reported. We describe a patient with symptomatic Zika virus infection in whom the virus was detected in semen for 92 days. Our findings support recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection

Checkley, AM

Gaskell, KM

Houlihan, C

Nastouli, E

UCL Discovery

 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 1, January 2017 137Katherine M. Gaskell, Catherine Houlihan,  Eleni Nastouli, Anna M. CheckleyZika virus is normally transmitted by mosquitos, but cases of sexual transmission have been reported. We describe a patient with symptomatic Zika virus infection in whom the virus was detected in semen for 92 days. Our findings sup-port recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection.Zika virus is a mosquito-transmitted flavivirus that was first isolated from mosquitos in the Zika Forest in Uganda. Since its introduction into Brazil in May 2015, the virus has spread rapidly through the Americas, and transmission is now widespread in South America, Cen-tral America, the Caribbean, the Pacific islands, Singapore, and Thailand (1). The virus is transmitted mainly by Ae-des aegypti mosquitos and causes symptoms in ≈20% of persons infected (2), usually manifesting as a mild illness consisting of fever, arthralgia, myalgia, conjunctivitis, and pruritic rash. Infection in pregnancy can lead to congenital Zika syndrome, which consists of multiple developmental abnormalities, including microcephaly and cerebral calcifi-cation, and fetal loss. Zika virus infection is also associated with Guillain-Barré syndrome (3).Although by far the most common route of Zika virus transmission is by mosquito, the virus can also be transmit-ted sexually (from male to female, female to male, and male to male) (4–8). Zika virus RNA has been detected in semen and vaginal fluid (9–12). We describe a case in which Zika virus persisted in semen for 92 days after symptom onset.The Study A previously healthy 45-year-old man became ill 1 day after returning to the United Kingdom from a 1-week holiday in Rio de Janeiro, Brazil, in February 2016. His illness lasted for 10 days and consisted of severe retro-orbital headache, arthralgia, myalgia, and high fevers, followed by a pruritic maculopapular rash. He had no symptoms of prostatitis or gross hematospermia. He had no history of immunocom-promise, and he was not on any regular medication. On day 3 of his illness, Zika virus RNA was detected in urine but not in serum; Zika virus IgM and IgG were not detected in serum by an ELISA IgM and IgG kit (EUROIMMUN AG, Lübeck, Germany) (13). Results of serologic testing for chikungunya, dengue, and yellow fever were negative by commercial assays. Seventeen days after the initial testing, Zika virus IgM and IgG were detected in a new serum sample from the pa-tient. The patient and his partner were planning to conceive and were reluctant to wait the 6 months recommended by Public Health England (1). Therefore, PCR for Zika virus RNA was performed on serial semen samples by using the Rare and Imported Pathogens Laboratory’s in-house real-time reverse transcription PCR (rRT-PCR), based on an as-say used by Pyke et al. (14). Zika virus RNA was detected 22, 55, and 92 days after symptom onset (cycle threshold values 21.3, 30.1, and 37.2, respectively). No microhema-tospermia was detected, and Zika virus could not be cul-tured at any point. No Zika virus RNA was detected in se-men at day 132 or day 174. The patient and his partner did not have unprotected sex during this period; his partner remained well and was not tested for Zika virus.ConclusionsIn this case, Zika virus RNA was detected in the semen of a previously healthy, immunocompetent adult who con-tracted his infection during a short visit to Rio de Janei-ro, Brazil, in February 2016. RNA was present in semen samples until 92 days after the onset of symptoms and was subsequently undetectable on 2 occasions.This report follows several others from the current out-break in which Zika virus RNA has been detected in semen >90 days after symptom onset in an immunocompetent and previously healthy adult. Previous reports include a man who had visited Haiti, in whom Zika virus RNA was persis-tently identified in semen until day 188 after symptom on-set (10). A subsequent report from Italy documented Zika virus RNA being persistently identified in semen until day 181 in a symptomatic traveler returning from Haiti (11). In these 2 cases, unlike the present case, disappearance from Persistent Zika Virus Detection in Semen  in a Traveler Returning to the  United Kingdom from Brazil, 2016 Author affiliations: University College London Hospital for Tropical Diseases, London, UK (K.M. Gaskell, A.M. Checkley); London School of Hygiene and Tropical Medicine, London (K.M. Gaskell); University College London Hospitals Department of Clinical  Virology, London (C. Houlihan, E. Nastouli); Department of Population, Policy and Practice, University College London Great Ormond Street Institute of Child Health, London (E. Nastouli)DOI: http://dx.doi.org/10.3201/eid2301.161300DISPATCHES138 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 1, January 2017semen was not demonstrated at a later point in time. In an-other case, Zika virus RNA was detected in semen 93 days after symptom onset; in that case, the patient had traveled to a nonepidemic area and had just been diagnosed with a sarcoma, and treatment including aggressive chemotherapy was planned (12). This subsequent treatment might have al-tered the kinetics of virus clearance. Further clarification on whether both symptomatic and asymptomatic patients can persistently shed Zika virus RNA in semen for prolonged periods is needed.This case is important because it reinforces the possi-bility raised by Nicastri et al. (10) that Zika virus might be sexually transmitted at later points in time than have been documented thus far. The longest known period between Zika virus infection and sexual transmission to another per-son is 31–42 days after onset of symptoms. It is unclear how the presence of Zika virus (or level of RNA) in se-men correlates to infectivity, or how long a person might be infectious by this route after infection with Zika virus. Guidelines from the World Health Organization, Public Health England, and the Centers for Disease Control and Prevention all recommend avoiding unprotected sex for 6 months after symptomatic Zika virus infection in a man (1,15). Published literature on sexual transmission and de-tection of Zika virus RNA in semen, including our report, supports these guidelines. As of press time for this article, published recommendations differ on how long to avoid unprotected sex in asymptomatic couples who have been potentially exposed to the virus.An important caveat, however, is that virus could not be cultured from semen samples from this patient or from the patients reported by Nicastri et al. (10) or Barzon et al. (11) at any point. This findings raise the possibility that the detection of RNA does not equate to the detection of infec-tious virus particles.An inability to detect Zika virus RNA in semen has been assumed to equate to a lack of infectivity by the sex-ual route (10,11). In this case, in which our patient and his partner planned to try to conceive, the results were useful in encouraging them to defer their plans until 2 sequential specimens were negative for Zika virus RNA. This delay, in fact, corresponded to 6 months after the onset of symp-toms, as recommended by current guidelines (1,15).Published studies report an enormous variability in how long after infection Zika virus RNA can be detected in semen, which makes advising patients on the risks for sexual transmission difficult. In this case, testing serial semen samples for evidence of Zika virus RNA helped guide patient management, and doing this routinely in returning travelers in non-Zika virus–endemic countries might be warranted. In such a context, a positive result should be interpreted as indicating possible ongoing risk for sexual transmission.Further studies on the kinetics of virus isolation and Zika virus RNA detection from semen are needed to help inform guidelines on Zika virus sexual transmission and how to manage the risks. These studies would be espe-cially useful in managing asymptomatic patients in whom evidence of Zika virus RNA detection, virus isolation, and sexual transmission is almost totally lacking.AcknowledgmentWe thank Emma Aarons for her helpful input and contributions to this article. Dr. Gaskell is a specialist registrar in infectious diseases at the Hospital for Tropical Diseases. Her primary research interests are structural health research in resource-poor settings,  multidrug-resistant tuberculosis, and tropical medicine. References  1. Public Health England. Zika virus (ZIKV): clinical and travel  guidance [cited 2016 Sep 5]. http://www.gov.uk/guidance/zika-virus  2. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL,  Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360:2536–43.  http://dx.doi.org/10.1056/NEJMoa0805715  3. Cao-Lormeau V-M, Blake A, Mons S, Lastère S, Roche C,  Vanhomwegen J, et al. Guillain-Barré syndrome outbreak  associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016;387:1531–9. http://dx.doi.org/10.1016/S0140-6736(16)00562-6  4. D’Ortenzio E, Matheron S, Yazdanpanah Y, de Lamballerie X, Hubert B, Piorkowski G, et al. Evidence of sexual  transmission of Zika virus. N Engl J Med. 2016;374:2195–8.  http://dx.doi.org/10.1056/NEJMc1604449  5. Oster AM, Russell K, Stryker JE, Friedman A, Kachur RE,  Petersen EE, et al. Update: interim guidance for prevention of  sexual transmission of Zika virus—United States, 2016.  MMWR Morb Mortal Wkly Rep. 2016;65:323–5.  http://dx.doi.org/10.15585/mmwr.mm6512e3  6. Davidson A, Slavinski S, Komoto K, Rakeman J, Weiss D.  Suspected female-to-male sexual transmission of Zika virus— New York City. MMWR Morb Mortal Wkly Rep. 2016;65:716–7. http://dx.doi.org/10.15585/mmwr.mm6528e2  7. Harrower J, Kiedrzynski T, Baker S, Upton A, Rahnama F,  Sherwood J, et al. 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Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after   Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 23, No. 1, January 2017 139Persistent Zika Virus Detection in Semen, UKreturning from Haiti to Italy, January 2016. Euro Surveill. 2016; 21:21. http://dx.doi.org/10.2807/1560-7917.ES.2016.21.32.30316 12. Mansuy JM, Pasquier C, Daudin M, Chapuy-Regaud S, Moinard N,  Chevreau C, et al. Zika virus in semen of a patient returning  from a non-epidemic area. Lancet Infect Dis. 2016;16:894–5. http://dx.doi.org/10.1016/S1473-3099(16)30153-013. EUROIMMUN. Zika: serological diagnostic tests available [cited 2016 Aug 5]. http://www.zika-diagnostics.com14. Pyke AT, Daly MT, Cameron JN, Moore PR, Taylor CT,  Hewitson GR, et al. Imported Zika virus infection from the Cook Islands into Australia, 2014. PLoS Curr. 2014;6:ecurrents.outbreaks.4635a54dbffba2156fb2fd76dc49f65e. http://dx.doi.org/10.1371/currents.outbreaks.4635a54dbffba2156fb2fd76dc49f65e15. World Health Organization. Prevention of sexual transmission  of Zika virus: interim guidance update [cited 2016 Sep 5].  http://www.who.int/csr/resources/publications/zika/sexual-transmission-prevention/enAddress for correspondence: Katherine M. Gaskell, University College London Hospitals NHS Foundation Trust, Infection Division, 235 Euston Rd, Fitzrovia London NW1 2BU, UK; email: kmgaskell@doctors.org.uk•  Waterborne Elizabethkingia meningoseptica in Adult Critical Care•  Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior•  Multiorgan WU Polyomavirus Infection  in Bone Marrow Transplant Recipient•  Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia•  Falling Plasmodium knowlesi Malaria Death Rate among Adults despite Rising Incidence, Sabah, Malaysia, 2010–2014•  Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014 •  Epidemiology of Haemophilus ducreyi Infections•  Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009–2013•  Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada •  Rapid Emergence and Clonal Dissemination of CTX-M-15–Producing Salmonella enterica Serotype Virchow, South Korea •  Avian Influenza A(H7N9) Virus Infection in 2 Travelers Returning from  China to Canada,  January 2015 •  Increase in Sexually Transmitted Infections among Men Who  Have Sex with Men, England, 2014 •  Surveillance of Bacterial Meningitis, Ethiopia, 2012–2013  •  Identification of Source of Brucella suis Infection in Human by Using Whole- Genome Sequencing, United States and Tonga •  Porcine Epidemic Diarrhea Virus and Discovery of a Recombinant Swine Enteric Coronavirus, Italy•  Seroepidemiology of Human Enterovirus 71 Infection among Children, Cambodia •  Outbreak of Panton-Valentine Leukocidin–Associated Methicillin-Susceptible Staphylococcus aureus Infection in a Rugby Team, France,  2010–2011 •  Variations in Spike Glycoprotein Gene  of MERS-CoV,  South Korea, 2015 •  Effectiveness of Ring Vaccination as Control Strategy for Ebola Virus Disease•  Autochthonous Nocardia cerradoensis Infection in Humans, Spain, 2011 and 2014 •  Asymptomatic Lymphogranuloma Venereum in Men who Have Sex with Men, United Kingdom •  Increased Risk for  ESBL-Producing Bacteria from  Co-administration of Loperamide and Antimicrobial Drugs for Travelers’ Diarrhea •  Hemagglutinin  Gene Clade 3C.2a Influenza A(H3N2) Viruses, Alachua County, Florida,  USA, 2014–15 http://wwwnc.cdc.gov/eid/articles/ issue/22/01/table-of-contentsJanuary 2016: Sexually Transmitted Infections

Persistent Zika Virus Detection in Semen in a Traveler Returning to the United Kingdom from Brazil, 2016

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Persistent Zika Virus Detection in Semen in a Traveler Returning to the United Kingdom from Brazil, 2016

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