Rift Valley Fever: The Next Big Threat to Pregnant Women?

It wasn’t long ago—2016, to be precise—that the specter of the Zika virus sent fear coursing through pregnant women, women trying to conceive, and their partners, particularly those living and traveling in areas where the Aedes aegypti mosquito is endemic. Now, scientists are raising the alarm about another mosquito-borne disease, Rift Valley fever (RVF), that they say could pose an even bigger risk to fetal health than Zika.

Mainly occurring in Africa and parts of the Middle East, the disease causes liver failure and/or the spontaneous miscarriage of fetuses in cattle. It typically infects just a few hundred humans annually.

Fever, joint pain, and headaches are hallmarks, although occasionally symptoms are more severe and affect the liver, eyesight, and brain. Published data on the disease outside of the livestock setting is sparse, which spurred a team of investigators at the University of Pittsburgh to conduct a study, published in Science Advances, on the virus in rats as well as in human placental tissue.

“There have only been 2 documented cases of confirmed vertical transmission in humans, 1 in Saudi Arabia and another...in Sudan,” Cynthia McMillen, PhD, a postdoctoral researcher in infectious diseases and microbiology at the University of Pittsburgh’s Center for Vaccine Research and an author of the recent study, told Contagion®. “In both cases, the mothers had symptoms of Rift Valley fever (fever, headache, malaise) during pregnancy and noticed similar symptoms in their newborn children shortly after delivery. Serology testing confirmed that the mothers and infants had RVF. Both infants developed severe hepatic disease; 1 died due to severe disease at 6 days old and the outcome of the infant from Sudan is unknown.”

Another study involved 130 women from Sudan. “[I]t showed that women with confirmed RVFV (Rift Valley fever virus) during pregnancy were 4.5 times more likely to have a miscarriage compared to uninfected women,” Dr. McMillen said. “Late-term miscarriage was also significantly associated with an acute RVFV infection. As of now, our knowledge is limited to these studies.”

When Dr. McMillen and her colleagues inoculated rats with Rift Valley fever virus, they observed a pattern of fetal death much like that seen in livestock. Barely more than a third (35.1%) of the babies born to the 11 infected rats survived, compared with 75% of the litter born to the 8 uninfected control rats. The placentas of the infected rats, both those that died and those that survived, were found to harbor elevated levels of the virus. The investigators were struck by the elevated levels of viral RNA found in the stillborn babies—10⁶ to 10⁷ PFU/ml eq.

The investigators also subjected human tissue samples obtained from women in their second trimester of pregnancy to strains of the virus, then monitored viral levels every 12 hours. High levels of the virus were found in the placenta, including in cells known as syncytiotrophoblasts.

According to Dr. McMillen, syncytiotrophoblasts are normally resistant to viral infection, including Zika, raising concerns that the Rift Valley fever virus may be an even more formidable threat.

“Our findings suggest that Rift Valley fever virus can overcome the antimicrobial barriers of the placenta, which typically protect the fetus from infection,” she said. Dr. McMillen was clear that more studies are needed, adding, “Infection of placental tissue at different stages of pregnancy would be an important next step to understand how RVFV infects the placenta at various stages of development.”

The World Health Organization (WHO) has prioritized Rift Valley fever for research and development initiatives. There is no commercially available vaccine for humans as of yet, and no cure. WHO recommends preventive measures including wearing gloves around sick livestock and using mosquito repellent and nets.