Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades?

Abstract

Zika virus (ZIKV) was identified as a teratogen in 2016 when an increase in severe microcephaly and other brain defects was observed in fetuses and newborns following outbreaks in French Polynesia (2013–2014) and Brazil (2015–2016) and among travelers to other countries experiencing outbreaks. Some have questioned why ZIKV was not recognized as a teratogen before these outbreaks: whether novel genetic changes in ZIKV had increased its teratogenicity or whether its association with birth defects had previously been undetected. Here we examine the evidence for these two possibilities. We describe evidence for specific mutations that arose before the French Polynesia outbreak that might have increased ZIKV teratogenicity. We also present information on children born with findings consistent with congenital Zika syndrome (CZS) as early as 2009 and epidemiological evidence that suggests increases in CZS‐type birth defects before 2013. We also explore reasons why a link between ZIKV and birth defects might have been missed, including issues with surveillance of ZIKV infections and of birth defects, challenges to ZIKV diagnostic testing, and the susceptibility of different populations to ZIKV infection at the time of pregnancy. Although it is not possible to prove definitively that ZIKV had teratogenic properties before 2013, several pieces of evidence support the hypothesis that its teratogenicity had been missed in the past. These findings emphasize the need for further investments in global surveillance for emerging infections and for birth defects so that infectious teratogens can be identified more expeditiously in the future.

The Antiviral Potential of AdipoRon, an Adiponectin Receptor Agonist, Reveals the Ability of Zika Virus to Deregulate Adiponectin Receptor Expression

“…Following worldwide Zika epidemics in the 2006–2016 period, and given the explosion of reported cases of adverse outcomes of pregnancies, congenital syndromes and birth defects (including about 2000 cases of ZIKV-linked microcephaly during the Brazilian outbreak [ 58 ], ZIKV must be considered a dangerous teratogenic pathogen [ 59 ]. Under these conditions, the search for antiviral drugs that can be administered to pregnant women living in ZIKV-endemic regions has become a challenge.…”

Editorial: Community series - innovative approaches in diagnosis of emerging/re-emerging infectious diseases, volume II

“…Several outbreaks of emerging infectious diseases and notably, the COVID-19 pandemic have had significant impacts throughout the 21 st century. Across multiple countries, each infection outbreak made a remarkable influence on population health and healthcare facilities, despite recent improved medical and diagnostic advances in countering disease epidemics: a high mortality rate was characteristic of the Ebola virus disease epidemic in 2012–2016 (Li et al, 2016 ; Forna et al, 2020 ), the teratogenic effects of Zika virus (ZIKV) were reported during the outbreak in French Polynesia in 2013–2014 and Brazil in 2015–2016 (Gilbert et al, 2023 ), and the highly contagious nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributed to its rapid spread and the global pandemic in 2020 (Mohapatra et al, 2020 ).…”