From Pages to Practice

By Karen Sokal-Gutierrez, MD, MPH, FAAP

Published April 11, 2018


A 30-year-old couple presents to their family physician to discuss their plan to try to get pregnant within the next year. The husband says, “My job has scheduled a 1-week business trip to Central America, but I’m worried about catching Zika and infecting my wife and future baby. Should I go on the business trip? If I catch Zika, how long do we need to wait before we try to get pregnant to avoid passing the disease?”

Since 2015–2016, the mosquito-borne Zika virus (ZIKV) has been recognized as a pandemic infection in 48 countries, including throughout the Americas. ZIKV infection in adults typically causes fever, rash, joint pain, and conjunctivitis. When women are infected with ZIKV during pregnancy, particularly in the first trimester, perinatal transmission can lead to fetal loss or congenital ZIKV infection and cause microcephaly, neuro-developmental, and ocular defects in the baby.

In addition to mosquito-borne and maternal-fetal ZIKV transmission, sexually-transmitted ZIKV has been documented — from men to women, women to men, and men to men. In ZIKV-infected men, ZIKV antigen and RNA have been found in spermatocytes and spermatozoa, as well as in sperm-free semen from vasectomized men. Questions remain regarding the infectivity of ZIKV-infected men: What is the frequency and duration of ZIKV shedding in semen and urine, and what factors reduce or prolong shedding in these fluids?

In this week’s NEJM, Mead et al. report the results of a prospective study of 184 adult men in the United States with symptomatic, laboratory-confirmed ZIKV infection. All but one of the men were infected with Zika during international travel; most reported rash, fever, joint pain, and conjunctivitis. Every 2 weeks for up to 6 months after the onset of their Zika illness, the men provided semen and urine specimens and completed a brief survey on urogenital symptoms and frequency of ejaculation. The specimens were tested for ZIKV RNA by real-time reverse-transcriptase polymerase chain reaction assay (RT-PCR) and positive samples were tested for infectious ZIKV by Vero cell culture and plaque assay. Participants whose specimens still tested positive for ZIKV RNA at the end of 6 months continued to submit samples until two consecutive samples tested negative.

ZIKV RNA was identified in semen in 33% of the 184 men. The proportion of men with ZIKV RNA shedding in semen was highest during the first 30 days after the onset of illness; 61% of the 36 men who submitted samples during that period tested positive. ZIKV shedding in semen decreased substantially during the subsequent months. The average time to clearance of ZIKV RNA from semen was 54 days. At 3 months, ZIKV RNA shedding in semen decreased to 7%. One man (<1%) continued to shed ZIKV for 9 months (281 days). In the semen samples with detectable ZIKV RNA, infectious ZIKV was isolated from 3 of 78 samples (4%), all of which were collected within 30 days of illness onset and all with at least 7.0 log10 ZIKV RNA copies per milliliter of semen.  Two of the 184 men (1%) were linked to cases of sexual transmission of ZIKV. Analysis of over 1,000 urine samples showed detectable ZIKV RNA in 8 (<1%).

Multivariate analysis showed a significantly shorter duration of ZIKV RNA shedding in semen was associated with the following factors: younger age, more frequent ejaculation, and specific characteristics of the illness (joint pain and absence of conjunctivitis).

The authors concluded that to prevent sexual transmission of ZIKV through semen, men who have symptoms of ZIKV infection should avoid unprotected sexual contact for 6 months after the onset of symptoms. Dr. Lindsey Baden, an Infectious Diseases specialist and Deputy Editor at NEJM commented, “Molecular methods allow us to more rapidly and accurately detect the presence of pathogens, such as Zika virus in semen. However, more investigation is needed to better determine how this correlates with infectivity.”

Returning to the couple, the physician should explain that the chances are low that the husband would become infected with Zika virus on a 1-week business trip to Central America. However, with a chance of catching symptomatic or asymptomatic infection and transmitting it sexually to his wife and unborn child, and the serious consequences of having a baby with congenital Zika infection, they may want to reconsider their plans by either going on the business trip and then abstaining from unprotected sex for 6 months or postponing the business trip until after their baby is born.

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Karen is a 2017-2018 NEJM Editorial Fellow, Clinical Professor at UC Berkeley-UCSF Joint Medical Program and UC Berkeley School of Public Health, researcher on children’s nutrition and oral health, and member of American Academy of Pediatrics.