While media coverage of Zika virus (“Zika”) has died down in recent months, the public health crisis is ongoing. In August 2016, we explored the background and history of Zika. Since that time, Zika has continued to spread and there have been a number of important discoveries about the virus.
Aedes Species Mosquito
Some emerging evidence suggests that Zika may lead to male reproductive tract damage and infertility. Recent laboratory research indicates that Zika persists in the testes and epididymis of male mice. Zika was able to damage these testicular and epididymal tissues, which led to lower testosterone levels and depleted sperm counts. Three weeks after infection, the testes of Zika-infected mice displayed markedly reduced size and weight. Zika in mice specifically infects sperm cells early in their development. The virus also infects and damages sertoli cells, which nourish developing sperm cells.
A similar study published in December 2016 confirmed that Zika induces inflammation of the testes and epididymis in mice, but not in the prostate or seminal vesicles. The study suggested that certain stem-like cells are vulnerable to Zika infection, which could explain why the virus can persist in the testes for long periods of time. The authors also presented evidence that Zika selectively infects the cells in the male reproductive tract that express a specific cell-surface receptor called AXL. This receptor is also present on neural stem cells, which suggests a possible mechanistic link between Zika-infected fetuses and developmental abnormalities like microcephaly.
Importantly, research suggests that damage to male testicular tissue was associated with infertility and an inability to successfully impregnate female mice. Therefore, men have been advised to take the same precautions that a pregnant woman would to avoid Zika infection. While these are laboratory studies that may or may not translate to human subjects, the results warrant continued investigation and suggest that vaccination to prevent Zika infection may be important for both men and women.
Sexual transmission of Zika presents a number of public health challenges. To date, a total of 38 sexually transmitted cases of Zika have been confirmed in the U.S. The risk of Zika transmission during sex remains unknown, and many more studies need to be performed. For example, researchers have not yet concluded how long Zika remains in semen or uncovered the mechanisms by which it infects sperm. Current data suggests that 50-60% of men have detectable levels of Zika RNA in their semen following infection. Sexual transmission via semen seems to occur predominantly when the male is symptomatic, but there are reports of asymptomatic men transmitting Zika as well. Determining the risk of sexual transmission of Zika is proving difficult in part because tests for Zika in semen are limited, and the virus is only detectable in blood for up to two months.
Based on the data currently available, the U.S. Centers for Disease Control and Prevention (“CDC”) has urged couples to wait to conceive following any possible Zika exposure. CDC guidelines suggest that females wait at least eight weeks after the resolution of symptoms (or the last possible exposure to Zika) before conceiving, while the recommendation for males is to avoid conception for at least six months. The CDC recommends either abstinence or diligent condom use as effective methods of preventing Zika transmission for couples that have been infected or traveled to high-risk areas.
The Spread of Zika
As of December 14, 2016, travel-related cases of Zika have been reported in every U.S. state except Alaska, as well as Washington D.C. and three U.S. territories (American Samoa, Puerto Rico, and the U.S. Virgin Islands). A total of 4,617 laboratory-confirmed Zika cases have been reported in the U.S. – 4,431 cases were travel-associated while the remaining 185 cases were acquired locally. Locally-acquired cases have now been reported in two locations, with 184 cases in South Florida and one recently reported case in Brownsville, Texas. Given that infection is asymptomatic in the majority of cases, there have likely been a number of additional cases that were not laboratory confirmed.
Zika is a serious public health concern because it is believed to cause congenital microcephaly and may cause other neurological disorders in newborns. As such, Zika cases in pregnant women are particularly concerning. As of December 13, 2016, laboratories have shown evidence of Zika infections in 1,246 pregnant women in the U.S. and 2,701 pregnant women in U.S. territories. In the U.S., there have been 34 infants with birth defects born to mothers with evidence of congenital Zika infection and an additional five pregnancies in which the fetus did not survive to term.
Zika in South Florida
Out of the 185 locally-acquired Zika infections in the U.S., all but one of them occurred in South Florida. The spread of Zika in South Florida began in the summer of 2016. On August 1, 2016, the CDC issued guidance urging pregnant women to avoid traveling to the Wynwood neighborhood in Miami after mosquito-borne spread of Zika was confirmed in the area. On August 19, a similar travel warning was issued that covered an area of Miami Beach. After 45 days without any local transmission, the guidance for the Wynwood area was downgraded. However, on October 13, mosquito-borne Zika transmission was reported in Little River, a Miami-Dade County neighborhood.
Shortly thereafter, the CDC updated its travel recommendations to cover all of Miami-Dade County. The county was divided into yellow areas, where local transmission had occurred but the risk was unknown, and red areas, where local transmission had recently been reported and the risk of acquiring Zika from a mosquito bite was deemed to be more substantial. As of December 9, 2016, the CDC has removed all of its red area designations, but all of Miami-Dade county remains classified as a yellow area.
Other Recent Research
A recent report published in the Journal of the American Medical Association put forth a preliminary estimate of the risk of Zika-related birth defects using preliminary data from the U.S. Zika Pregnancy Registry (“USZPR”). This report estimates that approximately 6% of congenital Zika infections result in birth defects. The risk is higher when the infection occurs during the first trimester – these cases carry an 11% risk of birth defects. Alarmingly, these rates are the same regardless of whether the infection is symptomatic or asymptomatic, highlighting the need for careful screening.
A separate study published in the CDC’s Emerging Infectious Diseases journal has discovered a possible explanation for the link between the Zika and microcephaly. The researchers investigated the placentas of mothers infected with Zika during pregnancy, as well as the brains of infants who died of microcephaly, with tests looking for Zika RNA. This study found that Zika replicates in the brain of fetuses with microcephaly. Surprisingly, the virus was found in both the fetal brain and the placenta for more than seven months after initial infection.
Zika Vaccine Program
VBI is applying its eVLP Platform in the development of a preventative Zika vaccine candidate. Enveloped virus-like particle (“eVLP”) vaccines closely mimic the structure of viruses found in nature, but without the viral genome, potentially yielding safer and more potent vaccine candidates. Preclinical testing suggests that VBI's Zika eVLPs may present Zika target proteins in an optimal shape and conformation, potentially allowing for a potent immune response. VBI plans to conduct additional testing in animal models to validate its approach.
To learn more, visit: https://www.vbivaccines.com/zika/.