Previous infection with dengue virus may provide cross-immunity against other flaviviruses and prevent symptomatic Zika virus infection, according to a study examining the incidence of infection among a cohort of Nicaraguan children.
Aubree Gordon, PhD, assistant professor of epidemiology at the University of Michigan School of Public Health, and colleagues wrote that zika virus (ZIKV) and dengue virus (DENV) share extensive homology, and infection with one serotype cross-protects against infection with others. However, the researchers wrote that there is a greater risk for severe dengue disease when a patient has sequential infection with different DENV serotypes — a process known as antibody-dependent enhancement, or ADE.
“Interestingly, throughout the Americas, a precipitous decrease in the number of dengue cases was observed following widespread Zika epidemics, suggesting that ZIKV infection might induce cross-protective immune responses against DENV,” Gordon and colleagues wrote. “However, the characterization of potential cross-protection between DENV and ZIKV requires knowledge of longitudinal preinfection immune histories, which is only available in prospective cohort studies.”
The researchers identified symptomatic ZIKV infections in a community-based cohort of about 3,700 children aged 2 to 14 years using real-time reverse transcription PCR testing and serology. Additionally, blood samples were collected annually to identify asymptomatic ZIKV infection.
Between Jan. 1, 2016, and Feb. 28, 3017, Gordon and colleagues identified 1,356 total ZIKV infections — 560 of which were symptomatic. The incidence of ZIKV infection was 14 symptomatic infections (95% CI, 12.9-15.2) and 36.5 total infections (95% CI, 34.7-38.6) per 100 person-years. The incidence of both symptomatic and asymptomatic infection was higher among females and older children.
Of those with ZIKV infection, 24.5% were infected at least once with DENV during patient follow-up. The researchers found an inverse relationship between symptomatic ZIKV infection and prior DENV infection in the entire cohort (incidence rate ratio = 0.63; 95% CI, 0.48-0.81; P < .005).
The risk for symptomatic ZIKV infection was reduced when children had recently been infected with DENV, the researchers said. This effect continued even after the researchers adjusted for age and sex but not when they adjusted for prior DENV infection. The total number of ZIKV infections was not affected by prior or recent DENV.
“Our findings might be generalizable to other locations that have had DENV circulation in the years preceding ZIKV circulation, including a great majority of countries in the Americas,” Gordon and colleagues wrote. “Conversely, it is possible that this cross-reactivity in the human immune response among closely related flaviviruses may be responsible for the dramatic decrease in dengue cases during and right after the Zika epidemic throughout the Americas.”
Other research has shown that the potency of ZIKV infection may be greater in patients who were previously exposed to DENV because of ADE — a link that may explain the extent of the last outbreak of Zika in the Americas. – by Katherine Bortz
Disclosures: The authors report no relevant financial disclosures.