Is dengue immune status a risk modifier for adverse fetal outcome in congenital Zika exposure?
Matthew Collins, MD, PhD
BACKGROUND: Zika virus infection during pregnancy causes a range of adverse fetal outcomes including microcephaly, growth restriction, fetal demise, arthrogryposis, and vision and hearing abnormalities – over 2500 congenital Zika cases have been reported in Latin America since 2015. Effective treatment or prevention methods are not yet available. Therefore, current prenatal care focuses on risk-stratification and monitoring of pregnant women.
GAP: It is unclear why mother-to-child transmission and birth defects occur in a subset of pregnant women infected by Zika or what risk factors are associated with adverse fetal outcomes.
Dengue is a related flavivirus, and cross-reactive but non-neutralizing antibodies from a first dengue infection increase the risk of severe diseases in a second dengue infection. There is evidence that this phenomenon may contribute to Zika pathogenesis, but it has not been proven in human cases or systematically investigated in population-based studies.
HYPOTHESIS: I hypothesize that risk of adverse fetal outcome with fetal Zika exposure is increased in mothers with prior immunity to dengue virus.
METHODS: We will perform a case-control study in a flavivirus-endemic area in Colombia among pregnant women with Zika infection. Exposures will be determined by advanced serologic techniques pioneered by our group for resolving complex antibody responses in individuals with multiple prior flavivirus infections.
IMPACT: This study will have immediate impact on public health policy as it is critical to determine whether DENV-immunity increases risk for adverse fetal outcomes in order to provide appropriate family planning counseling in the setting of ZIKV infection. With improved understanding of risk for adverse fetal outcomes, providers can counsel women and couples living in or traveling to ZIKV-endemic areas on an individual basis during important and sometimes difficult decisions prior to or during pregnancy. These findings will also inform policy decisions about deployment of DENV vaccination, which is being tested widely in Asia and Latin America.
Optional/Additional Comments: We appreciate the support of the Thrasher Research Fund in this important area of investigation. The recent Zika epidemic has had a dramatic impact on millions globally, particularly women and their partners that are expecting or caring for newborn children. While many questions remain, there are a set of solvable problem related to Zika that can improve our public health response to this emerging pathogen.