Prior Dengue Infection in Pregnant Women May Increase Risk of Severe Zika in Their Babies

A pair of new studies are giving insight into how a previous infection with Dengue virus in pregnant women may increase the risk of severe Zika virus infection in their infants, and vice versa, which may be significant in areas where both flaviviruses are prevalent.

Dengue and Zika virus can be transmitted to humans from certain ticks and mosquitoes. Dengue is a disease that causes flu-like illness but repeated infections with the virus can lead to a lethal condition known as severe dengue, a leading cause of serious illness and death among children in some Asian and Latin American countries according to the World Health Organization (WHO). Each year an estimated 500,000 people with severe dengue require hospitalization, and about 2.5% die of the illness.

Individuals with Zika virus infections typically experience no symptoms or mild symptoms, but in pregnant women, the virus can lead to congenital Zika syndrome, marked by microcephaly and other birth defects.

Two new studies published on November 15, 2018, in the journal Cell Host & Microbe are shedding new light on how the antibodies of these 2 flaviviruses can impact infection with one another.

The first study, led by investigators from Emory University, indicates that pregnant mothers with prior Dengue infection may have infants who are at greater risk of severe Zika. To study the mechanisms of transplacental transmission of Zika virus, the investigators exposed donated placental tissue to Dengue antibodies and the Zika virus. They found that although the antibodies bound to the virus, they failed to neutralize Zika and instead moved the virus into the placenta cells.

In the second paper, investigators from the La Jolla Institute for Immunology studied the mouse pups of mothers with circulating Zika antibodies. They found that although mothers passed these antibodies onto their pups, thereby reducing their risk for Zika infection, the Zika antibodies attached to Dengue in pups exposed to the virus and put them at higher risk for deadly infections than in pups born to mothers without Zika antibodies.

Both studies indicate that with the cross-reactivity between the 2 viruses and their antibodies, the presence of antibodies for 1 virus assist the other virus to more easily enter placental macrophages.

"There's a prevailing attitude that antibodies are always good, but antibodies can have a range of effects," co-first author Sujan Shresta, PhD, said in a recent statement. "We need to embrace this complexity to develop the most effective vaccines."

With a dengue vaccine moving closer to approval by the US Food and Drug Administration (FDA) and clinical trials underway for a Zika vaccine candidate, the results of the new studies indicate that vaccinating to prevent 1 disease may inadvertently increase susceptibility to the other, which may raise flags in regions where both viruses are endemic.

In an interview with Contagion®, Emory researcher Mehul Suthar, PhD, addressed the challenges in researching this cross-reactivity between the viruses within populations.

“We know that there is a significant population that lives where both Zika virus and Dengue virus co-circulate. During the epidemic, there were many pregnant women exposed to Zika virus that live within Dengue-endemic regions,” Dr. Suthar said. “A retrospective study is challenging because some of the antibodies to Dengue can bind to Zika virus. As a matter of fact, this is one of the reasons why it was so difficult to rapidly develop Zika virus-specific diagnostics. “

The studies’ authors say their findings on these complicated immune responses should be considered as vaccines for Dengue and Zika are in the pipeline and highlight the need for research on how other flaviviruses may interact to impact mothers and their babies.