Prolonged Maternal Zika Viremia as a Marker of Adverse Perinatal Outcomes

Abstract

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal–fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus–infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January–July 2016. Prolonged viremia was defined as ongoing virus detection > 30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9–57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0–15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9–5.5]).

Neonatal Development in Prenatally Zika Virus-Exposed Infant Macaques with Dengue Immunity

“…There were no other maternal ZIKV infection characteristics or pregnancy parameters that predicted developmental outcomes as consistently as maternal ZIKV viremia duration did. Our finding that shorter maternal viremia duration is associated with better development extends what is known from human studies, which is that shorter maternal viremia duration is associated with lower rates of fetal demise and infant cerebral abnormalities [ 41 ]. Thus, shortening maternal viremia duration improves pregnancy outcomes and infant developmental outcomes in human and preclinical model studies, respectively, and should be considered a target for new ZIKV antivirals.…”

Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus

“…The unusually short time to peak viremia (approximately 2 days) observed following our high-dose SQ inoculations artificially shortens therapeutic window, which is typically 5 days for mosquito to macaque ZIKV transmission (26). However, use of therapeutics after 30 days can improve infection outcomes in unique cases of prolonged viremia (27).…”

“…The unusually short time to peak viremia (approximately 2 days) observed following our high-dose SQ inoculations artificially shortens therapeutic window, which is typically 5 days for mosquito to macaque ZIKV transmission (26). However, use of therapeutics after 30 days can improve infection outcomes in unique cases of prolonged viremia (27). It should be noted that even if this model is not ideal for testing post-exposure therapeutics, it may still be valuable for unpacking mechanisms of fetal demise and understanding the neurologic impact of ZIKV-DAK on surviving infants with in utero exposure.…”

Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

“…Maternal Zika virus (ZIKV) infection is associated with adverse pregnancy outcomes including pregnancy loss and fetal malformations 1,2 . Prolonged maternal viremia in humans and nonhuman primates 2-7 suggests there is a pregnancy-specific viral reservoir, and the presence of virus at the maternal fetal interface 8 support the premise that the placenta may serve as a viral reservoir. Thus, there is a pressing need to better understand the mechanisms of placental infection and ZIKV impact on placental cell function.…”