Clinical Practice in the New Era of Global Pandemics
The devastating fetal and neurologic complications of Zika underscore the need for studies of immunity and viral persistence during acute infections to inform development of countermeasures such as vaccines, treatments, and improved diagnostics. Acute immune responses are critical determinants of viral disease outcomes. In 2016 we had a unique opportunity to care for and study five returned US travelers or expatriates who had molecularly confirmed acute Zika. This permitted examination of the antiviral roles of innate and adaptive immunity.
Quantitative assays characterized immune responses and Zika virus (ZIKV) RNA. Two patients were pregnant and had plasma viral RNA detectable for >26 and >44 days after symptom onset. Acute Zika patients including the pregnant women mounted strong innate, B cell, antibody, and T cell activation responses but functional CD8+ T cells targeting viral structural proteins were rarely detected despite profound CD8+ T cell activation. Even with prolonged maternal viremia both pregnancies resulted in live births of apparently healthy babies. The cross-reactive immune response from prior flavivirus infections (e.g., dengue) or vaccinations (e.g., yellow fever vaccine) altered the immune profile and may have reduced peak ZIKV viremia. Larger studies of acute Zika are needed to confirm and extend these results but it is challenging to enroll these patients at very early time-points.
Early education of clinicians, public health officials, and the public are essential immediate components of epidemic response – even when facts and data are few. Ongoing surveillance and epidemiologic investigations are essential to build the data bases of facts needed. Rapid response platforms for biomedical clinical studies and development of countermeasures are needed. Response times need to be shortened in order to optimize the impact of interventions to fight pandemics.
The author wishes to thank the study volunteers for their generous contributions of time and participation. This work was supported by Emory University School of Medicine including its Department of Medicine and Division of Infectious Diseases; the Emory Vaccine Center; and the Georgia Research Alliance. We appreciate the contributions of Georgia Department of Public Health.