The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention1,2, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).

Population based serological surveys are the gold-standard to quantify dengue (DENV) transmission. The purpose of this study was to estimate the age-specific seroprevalence and the force of infection of DENV in an endemic area of Colombia. Between July and October 2014, we conducted a household based cross-sectional survey among 1.037 individuals aged 2 to 40 years living in 40 randomly selected locations in urban Piedecuesta, Santander, Colombia. In addition, we also enrolled 246 indviduals living in rural “veredas”. Participants were asked to answer a questionnaire that included demographic, socioeconomic and environmental questions and to provide a 5 ml blood sample. Sera were tested using the IgG indirect ELISA (Panbio) kit to determine past DENV infection. The overall DENV seroprevalence was 70% (95% CI = 67%-71%), but was significantly higher in urban (81%, 95% CI = 78%-83%) as compared to rural (21%, 95% CI = 17%-27%) locations. Age was a major predictor of seropositivity, consistent with endemic circulation of the virus. Using catalytic models we estimated that on average, 12% (95%CI = 11%-13%) of susceptible individuals living in the city are infected by DENV each year. Beyond age, the only predictor of seropositivity in urban locations was prior history of dengue diagnosed by a physician (aPR 1.15, 95% CI = 0.98–1.35). Among participants living in rural settings, those that reported traveling outside of their vereda were more likely to be seropositive (aPR 3.60, 95%CI = 1.54–8.42) as well as those who were born outside of Santander department (aPR = 2.77, 95%CI = 1.20–6.37). These results are consistent with long term endemic circulation of DENV in Piedecuesta, with large heterogeneities between urban and rural areas located just a few kilometers apart. Design of DENV control interventions, including vaccination, will need to consider this fine scale spatial heterogeneity.

Broad consent for future use facilitates the reuse of participant-level data and samples, which can conserve limited resources by confirming research findings and facilitate the development and evaluation of public health and clinical advances. Ethics review committees (ERCs) have to balance different stakeholder concerns when evaluating the risks and benefits associated with broad consent for future use. In this qualitative study, we evaluated ERC members’ concerns about different aspects of broad consent, including appropriate governance, community engagement, evaluation of risks and benefits, and communication of broad consent for future use in Colombia, which does not currently have national guidance related to broad consent for future use. We conducted semi-structured, in-depth interviews with 24 ERC members from nine Colombian ERCs. We used thematic analysis to explore ERC members’ concerns related to broad consent for future use. Most ERC members expressed concern about the idea of not specifying the purposes for which data would be used and by whom and suggested that pre-specifying governance procedures and structure would address some of their concerns about broad consent. ERC members emphasized the need for engaging communities and ensuring research participants understood broad consent for future use-related language in informed consent forms. Researchers and research institutions are under increasing pressure to share public health-related data. ERC members play a central role in balancing the priorities of different stakeholders and maintaining their community’s trust in public health research. Further work is needed on guidelines for developing language around broad consent, evaluating community preferences related to data sharing, and developing standards for describing governance for data or sample sharing in the research protocol to address ERC members’ concerns around broad consent for future use.