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A global alliance for Zika virus control and prevention

Periodic Reporting for period 3 - ZIKAlliance (A global alliance for Zika virus control and prevention)

Reporting period: 2019-10-01 to 2021-03-31

ZIKAlliance is a multinational, multi-disciplinary research consortium comprised of 54 partners worldwide. It investigates clinical, fundamental, environmental and social aspects of ZIKV infection, in particular the impact of Zika virus (ZIKV) infection during pregnancy (including short and medium term effects on newborns). The objectives are (i) to improve the scientific knowledge about ZIKV natural history, mechanisms of infection, immune response, diagnostic methods, potential antiviral treatments and societal impact and (ii) to build preparedness capacity for future epidemic threats in Latin America and the Caribbean.
Regarding the clinical research, important pregnant women (PW) and children (CH) cohorts have been set-up and are ongoing in 14 sites in 8 countries in Latin America and the Caribbean. To harmonize the laboratory results from the clinical cohort, reference laboratory support for the cohort studies have been established.

Basic research provided detailed information on virus molecular epidemiology and phylogeography and on the replication cycle of ZIKV in various cell culture and animal model systems. Innovative search tools have been developed, and we have identified a variety of host factors that are involved in ZIKV replication. We have studied maternal-fetal transmission of ZIKV and infection of placenta and fetuses in animal models and humans and identified mechanisms leading to sexual transmission of ZIKV and to neurodevelopmental defects associated with fetal infection. We have also identified a human host factor essential for ZIKV infection of placental cells.

Regarding environmental studies, more than 4000 animal specimens from over 20 wild and domestic animal species have been collected and tested for ZIKV. Experimental infections of monocyte-derived cells from diverse animal species were performed using multiple flaviviruses including Zika virus and provided limited evidence for Zika virus sylvatic cycles in the Americas. In contrast, sylvatic cycles for yellow fever virus were described in non-human primates, and new animal reservoirs were identified for other potential arboviruses. When studying mosquito populations, we have successfully detected ZIKV in field-collected mosquitoes using mass screening methods. This work and experimental vector competence studies contributed to establish the pivotal role of aedes mosquitoes in transmission, in particular Ae. aegypti. Since main ZIKV vectors are resistant to most commonly used insecticides in the Americas, we have investigated the development of promising bio-tools to improve vector control. Finally, it was also shown that co-infections of ZIKV with other arboviruses tends to modify viral evolution and mosquito antiviral responses.

Regarding social sciences, we developed a historical, epistemological and political timeline of Zika epidemic and response in Brazil through interviews, public documents, epidemiological and socio-economic data analysis, as well as the public understanding of Zika infection and social imaginary in social media and in some selected regions in Brazil.

Communication to the scientific community was ensured through the publication of press releases, a website, a twitter channel, an open access repository with all articles published within the consortium and one consortium newsletter. We have contributed to the publication of five cross-consortia newsletters, and we have worked to ensure that all ZIKAlliance-related external activities (annual meetings, conferences, etc.) and scientific outputs (journal articles, commentaries) have received maximum exposure and public acknowledgement.

Early protocol versions for the PW and CH cohorts were exchanged between the three EC Consortia soon after the projects were granted funding. A data harmonization meeting was held in early 2017 with representatives from the three EC funded ZIKA consortia. To promote harmonized a multicentric research in the context of an epidemic, external quality assessment (EQA) for molecular testing was carried out first within ZIKAlliance despite significant administrative and regulatory barriers. In addition, the challenges faced in the three EC-funded Zika consortia with regard to harmonization and data sharing led researchers from ZIKAlliance to seek additional funding. They successfully secured funding from the EC H2020 programme in a personalized medicine call with the project ‘ReCoDID’ – Reconciliation of Cohort Data for Infectious Diseases.
We must be prepared to follow the children longer than initially projected. The Toxoplasmosis and CMV research communities were able to follow their children cohorts up to 10 years and some children only developed abnormalities after years of observation. We have to make use of the opportunities that we currently have now and follow up the children cohorts as long as possible to detect late-stage abnormalities and potential differences in cognitive development to assess the true impact of the ZIKV epidemic.
We have been successful in developing several assays and diagnostic algorithms for the identification of ZIKV patients. Different serological methods have been established to assess the flavivirus immune status of patients, and potential biomarkers and susceptibility genes for complications associated with ZIKV infection are under investigation.
We successfully detected limited Zika virus exposure, but evidence to other potentially important arboviruses of livestock and wild animals in Latin America. Indeed, the work carried out on the overall period allowed to highlight the main ZIKV vectors by detecting ZIKV in field-collected mosquitoes and testing their vector competence in lab conditions.
Completion of the project will allow understanding maternal-foetal transmission mechanisms, and mechanisms of neurodevelopmental defects associated with foetal ZIKV infection and sexual transmission mechanisms of ZIKV. Identification human host factors critical for ZIKV replication will lead to discover potential therapeutic targets.
The Social Sciences work has continued its activities to influence national and international health authorities, national and international research funders, and supporting social movements to respond to Zika epidemic in Brazil and its social and economic repercussions, with the medium-term objective of promoting innovation on preparedness, response and post-epidemic planning to Zika and other emerging and re-emerging diseases.
For the remaining year of the project, we expect to increase public engagement of ZIKAlliance with the broader scientific community via social media, the website and the newsletter.
The harmonization efforts between the three EC-funded Zika research consortia leverage efforts by the WHO moderated ‘Individual Patient Data Meta-Analysis’. In this effort, the three EC-funded Zika Consortia plus other Zika cohort studies convened to harmonize their studies so that they can be analysed in a pooled data set in the future. The study design of the IPD-MA was published with important input from the three EC-funded consortia.
Figure showing the worldwide distribution of ZIKAlliance partners
Figure showing countries and territories in the Americas with confirmed autochthonous ZIKA cases
Logo of the project
Diagram of the 12 ZIKAlliance WPs