Detecting Vertical Zika Transmission: Emerging Diagnostic Approaches for an Emerged Flavivirus

Zika virus (Zika) was recently responsible for a massive epidemic that spread throughout Latin America and beyond. Though Zika is typically asymptomatic or self-limiting, the sheer numbers of Zika infections led to the identification of unexpected phenotypes including sexual transmission, Guillain-Barré syndrome, and teratogenicity. Thousands of infants in South, Central, and North America have now been born with microcephaly or one of a number of fetal anomalies constituting the congenital Zika syndrome (CZS). Diagnosing CZS is based on a combination of clinical risk assessment and laboratory testing (which includes determining whether the mother has experienced a possible Zika infection during her pregnancy). A newborn suspected of having congenital Zika infection (due to maternal Zika infection or a birth defect described in association with congenital Zika infection) is then specifically tested for presence of Zika virus in neonatal tissue or anti-Zika IgM in the blood or cerebrospinal fluid. Though the guidelines are clear, there is room for considerable practice variation to emerge from individualized patient-provider encounters, largely due to limitations in diagnostic testing for Zika. The natural history of Zika further obscures our ability to know who, when, and how to test. Molecular diagnostics are highly specific but may not serve well those with asymptomatic infection. Serologic assays expand the diagnostic window but are complicated by cross-reactivity among related flaviviruses and passive immunity transferred from mother to baby. Furthermore, existing and emerging diagnostic tools may not be widely available due to limitations in resources and infrastructure of health systems in affected areas. Improvements in assay parameters as well as advances in platforms and deployability hold promise for optimizing diagnostic approaches for congenital Zika infection. The diagnostic tools and technologies under development must be integrated with forthcoming clinical knowledge of congenital Zika infection to fully realize the value that laboratory testing holds for diagnosing in utero mother to child transmission but also for understanding, predicting, and managing the health outcomes due to congenital Zika infection.