Paniagua-Avila, Alejandra, Olson, Daniel, Connery, Amy, Calvimontes, D. Mirella, Bolanos, Guillermo A., Lamb, Molly M., Bauer, Desiree, Ralda, Aida, Rojop, Neudy, Barrios, Eduardo, Chacon, Andrea, Gomez, Melissa, Arroyave, Paola, Hernandez, Sara, Martinez, Maria Alejandra, Bunge-Montes, Saskia, Colbert, Alison, Arias, Kareen, Brazeale, Garret, and Holliday, Andrea
During the course of the 2015–2017 outbreak of Zika virus (ZIKV) in the Americas, the emerging virus was recognized as a congenital infection that could damage the developing brain. As the Latin American ZIKV outbreak advanced, the scientific and public health community questioned if this newly recognized neurotropic flavivirus could affect the developing brain of infants and young children infected after birth. We report here the study design, methods and the challenges and lessons learned from the rapid operationalization of a prospective natural history cohort study aimed at evaluating the potential neurological and neurodevelopmental effects of postnatal ZIKV infection in infants and young children, which had become epidemic in Central America. This study enrolled a cohort of 500 mothers and their infants, along with nearly 400 children 1.5–3.5 years of age who were born during the initial phase of the ZIKV epidemic in a rural area of Guatemala. Our solutions and lessons learned while tackling real-life challenges may serve as a guide to other researchers carrying out studies of emerging infectious diseases of public health priority in resource-constrained settings. Author summary: During the 2015–17 Zika outbreak in the Americas, many research sites struggled to rapidly establish cohorts to study the neurodevelopmental outcomes of exposed infants and children, due to both logistical difficulties and a lack of appropriately adapted/validated neurodevelopmental tools. During this time period, we conducted a study evaluating the neurodevelopmental outcomes of post-natal ZIKV and dengue virus (DENV) infection among of infants (<3 months at enrollment) and children (1.5–3.5 years at enrollment) at a site in rural, southwest Guatemala. The study, which enrolled a cohort of 500 mother-infant pairs and 400 children, was a collaborative effort that leveraged expertise at multiple institutions to rapidly implement a study protocol in a resource-limited region of Guatemala. In this Methods paper, we describe the study methodology, how we implemented our research protocol in this rural, resource-limited community, and challenges and lessons learned during its operationalization. Specifically, we address how we adapted neurodevelopmental testing tools to the local language and cultural context, trained and managed a research team recruited from the local community, maintained competency and quality control in this workforce, developed critical laboratory infrastructure, and engaged with local community stakeholders. Our approach may serve as a guide to other researchers carrying out future studies focusing on child neurodevelopment as well as clinical evaluation of ZIKV and other emerging infectious diseases of public health priority. [ABSTRACT FROM AUTHOR]