A History With Dengue Fever May Provide Some Protection From Symptomatic Zika

Immunity from prior dengue fever infection appeared to provide some protection against symptomatic Zika disease, investigators studying a pediatric cohort in Nicaragua were surprised to find.

The team had wondered whether a prior dengue infection might aggravate Zika, but after tracking a group of 3000 children aged 2 to 14 years for 15 years, they determined that kids who had previously had a dengue infection were significantly less likely to be symptomatic when infected with Zika.

The study, published recently in PLOS Medicine, followed approximately 3700 children and screened them annually for Zika, both symptomatic and clinically inapparent. Between January 1, 2016, and February 28, 2017, investigators noted 1356 total Zika infections, 560 of them symptomatic.

Investigators from the University of Michigan; the University of California, Berkeley; the Ministry of Health in Managua, Nicaragua; and Managua’s Sustainable Sciences Institute used multivariable Poisson regression to determine the relation between prior dengue fever infection and incidence of symptomatic Zika disease in 3027 of the participants with documented dengue immunity.

“Prior DENV infection was inversely associated with risk of symptomatic ZIKV infection in the total cohort population (incidence rate ratio [IRR]: 0.63; 95% CI: 0.48, 0.81; p < 0.005) and with risk of symptomatic presentation given ZIKV infection (IRR: 0.62; 95% CI: 0.44, 0.86) when adjusted for age, sex, and recent DENV infection (1—2 years before ZIKV infection),” investigators wrote. “Recent DENV infection was significantly associated with decreased risk of symptomatic ZIKV infection when adjusted for age and sex, but not when adjusted for prior DENV infection. Prior or recent DENV infection did not affect the rate of total ZIKV infections.”

The potential cross-protection between dengue and Zika is worthy of more research and could substantially change the research and development landscape for vaccines.

“The potential protection that we have observed is important for vaccine development for both dengue virus and Zika virus,” Aubree Gordon, PhD, assistant professor in the Department of Epidemiology at University of Michigan’s School of Public Health and co-author of the study, told Contagion^®.

“If dengue immunity protects from Zika, it is entirely possible that Zika immunity may protect from dengue. And, it is possible that there may not only be cross-protection, but there also could be enhancement of disease. Potential cross-protection or enhancement of disease severity will be important issues to examine in vaccine development and evaluation,” she continued.

Dr. Gordon also believes more research is needed on the possibility of dengue antibodies enhancing or aggravating Zika.

“We plan to examine if there are specific levels of dengue virus antibody titers that are protective,” Dr. Gordon said. “In addition, although in our current study we only saw protection, more work is required to examine for potential enhancement of Zika disease by dengue antibodies."

Lionel Gresh, PhD, who led the field studies on the ground in Nicaragua and co-authored the study, told Contagion^® the team also plans to examine whether the protection works the other way around.

"We would like to investigate if cross-protection also works the other way around, if a prior Zika virus infection might protect against symptomatic dengue, and our cohort study in Nicaragua has the setup to do this in the near future," he said.

The research was funded in part by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.