Recently, officials reported a dramatic increase in the number of babies in New York City who either tested positive for the mosquito-borne Zika virus or were diagnosed with the characteristic developmental symptoms in the brain that are closely associated with the infection. The same day, a medical journal published research by a team of scientists at the University of Wisconsin-Madison (UW) that suggests we may have underestimated the threat posed by Zika—in terms of both the number of pregnant women who may become infected and the scope of the symptoms that may present after delivery.

Zika was widely recognized as a public health crisis in 2014 after Brazilian doctors linked the virus to a dramatic uptick in the number of babies born with a severe birth defect in the brain called microcephaly. The relationship between Zika and congenital brain defects was confirmed in 2016 by researchers working with mouse models, thereby building on earlier findings from studies with animals that showed how the virus works as a neurotropic agent (by attacking the nervous system). With these findings, the research community could now rule out other theories about a potential causal role played by cofactors (like insecticides) in microcephaly cases—and could also better explain one of the more common avenues of human-to-human Zika transmission, by which pregnant women are initially infected by mosquitoes and the virus is spread to the fetus during pregnancy (or to the newborn during delivery).

Illustration depicts common symptoms associated with microcephaly

The birth defects in many cases of microcephaly are jarring. Newborns often have tiny skulls, receding foreheads, loose scalps—and most will suffer from severe, lifelong intellectual disability. And this represents just one of the reasons that the virus has become a global public health emergency. Adults bitten by infected mosquitoes can develop a severe and potentially lethal disorder of the central nervous system called Guillain-Barre´ syndrome. Making matters worse, researchers still don’t know very much about other modes of human-to-human Zika transmission, so the risk of infection is largely unknown for people living in affected areas. And two months after infection, during which period a patient may in some cases be asymptomatic, Zika in the bloodstream drops below detectable levels. This information brings into sharp relief last week’s news of more cases discovered in New York’s labor and delivery units—the city reported nearly seven times more cases of infected newborns compared to figures from December of 2016. “For pregnant women and their babies,” warned Deputy Mayor of Health and Human Services Dr. Herminia Palacio, “the threat is real and the threat is lifelong.”

Breakthroughs, like those published last week by the UW team from their studies with rhesus macaques, have armed public health officials and the research community with a more comprehensive understanding of the danger posed by Zika. “It’s sobering,” said UW researcher Ted Golos. “If microcephaly is the tip of the iceberg for babies infected in pregnancy, the rest of the iceberg may be bigger than we’ve imagined.” Golos and his team determined that infected pregnant monkeys pass the virus to their fetuses in a manner that is consistent with and nearly identical to that which occurs in human pregnancies, damaging every part of the interface between mother and baby (the placenta, amniotic fluid, and uterine lining) while causing ocular inflammation and tissue damage. Newborn monkeys developed problems stemming from Zika infection including chorioretinal atrophy and microphthalmia (in which the eye doesn’t grow to the expected size), suggesting that symptoms in human babies infected with the virus may extend well beyond the congenital brain defects that Brazilian doctors first observed three years ago.

UW researchers note that animal models will continue to play a crucial role, provided the similarities in how Zika is transmitted, how the infection progresses, and the nature of pregnancy complications that have been observed in humans and monkeys. This shared genetic makeup, between people and nonhuman primates, has historically led to breakthroughs in the body of medical knowledge regarding infectious disease, as well as lifesaving treatments for conditions like HIV. And many of the conclusions about Zika that were yielded by studies with macaques could not have been reached from research with pregnant humans, certainly not quickly enough to make a difference for people who are infected. The need for new research to fill existing knowledge gaps is greater than ever, as Zika has spread to mosquitoes in the United States, and therefore also to patients who did not travel internationally in countries with high numbers of infected insects.

Zika can also be transmitted sexually, but until recently, researchers knew very little about the risks associated with infected sperm. Studies with mice in 2016 led to important conclusions about how long the virus can live in seminal fluid, prompting the Centers for Disease Control and Prevention to issue warnings against sperm donation for men who live in three Miami-area counties. (Among the 221 patients in the United States who were infected by American mosquitoes and tested positive for Zika, all but six live in South Florida.) Adding to the threat of infection, sexually transmitted or otherwise, emerging evidence from studies with male mice suggests that the virus can damage the male reproductive tract, potentially causing infertility. These developments have both strengthened efforts to reduce the risk of infection, especially among women who are pregnant (or trying to become pregnant), and expanded the purview of researchers to include the virus’s potential threat to tissue in the reproductive organs.

The focus of investigators working to mitigate this public health emergency will continue to evolve with new information gleaned from studies with animal models, studies that have already forged a path toward testing new vaccines and treatments. For example, working with pregnant mice, a team of researchers at the Washington University School of Medicine have demonstrated that a drug used to treat Malaria in pregnant women protects the fetus from infection with Zika.

These new frontiers in research and biomedical science can offer a future, or in many cases a different, healthier future, for unborn babies infected with Zika; for pregnant women living in countries—many of them very poor—that have high numbers of infected mosquitoes; for sexually active men who live in South Florida; and, perhaps most strikingly, for an unknown number of uninfected people whose risk is not yet fully understood by the medical research community.

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