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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - ZIKAlliance (A global alliance for Zika virus control and prevention)

Teaser

Summary

ZIKAlliance is a multinational, multi-disciplinary research consortium comprised of 54 partners worldwide. The project investigates clinical, fundamental, environmental and social aspects of ZIKV infection.
ZIKAlliance has 4 key study objectives: the impact of Zika virus (ZIKV) infection during pregnancy (including short and medium term effects on newborns); the natural history of ZIKV infection in humans and their environment in the context of other circulating arboviruses; improving scientific knowledge about ZIKV, mechanisms of infection, immune response, diagnostic methods, potential antiviral treatments; building preparedness capacity for future epidemic threats in Latin America and the Caribbean.

Work performed

In the domain of clinical research, Pregnant Women (PW) & Children (CH) cohorts are ongoing (11 sites and 7 countries in Latin America & the Caribbean). Another cohort (or group) of PWs was included via pre-existing protocols. We found high variability in new-born head circumference from infected pregnant women in Asia & Africa. Mitigating measures and tools to improve data analysis are currently discussed to address this issue. Regarding diagnosis of ZIKV infection, laboratory capacity was examined and the main barriers reported in a lessons learned paper. Initial procedures were adapted to ease pooled analysis from different sites. Using epidemiology data and modelling research, we created a pan-continental ZIKV model to project realistic case numbers.

In the domain of basic research, we have published several studies focussed on ZIKV replication biology (using viruses of diverse origins), improved the virus replication models and identified major factors involved in the entry of the virus in the cells. The virus genetic studies allowed improving annotated sequence datasets, ZIKV phylogeny and specifying the date on which ZIKV reached the Americas. A large number or diagnostic and research tools (e.g. antigens, antibodies and reverse genetics methods) were developed. We are currently working on the identification and development of ZIKV inhibitors using screening methods and animal models. Working on the effect of ZIKV on the neural development system, we have identified major determinants of ZIKV-induced microcephaly. Additional work on ZIKV sexual transmission is ongoing.

Environmental studies allowed sampling ~4000 animal specimens (>20 species). We found limited evidence for infection of (peri)urban primates with ZIKV & Chikungunya virus. Multiple parallel sylvatic cycles were observed during the recent Brazil yellow fever outbreak. We have set up in vitro systems to investigate flaviviruses using animal primary cells. Large entomology studies were performed. From ~13,800 mosquitoes from epidemic regions, ZIKV was found only in Ae. aegypti mosquitoes. We found that Ae. aegypti from epidemic regions are highly susceptible to the 3 ZIKV genotypes (Asian, African, American) whilst Ae. albopictus from France are more susceptible to the African genotype. The antiviral response in mosquitoes was investigated and 8 mosquito factors affecting ZIKV replication identified. We observed various levels of Ae. aegypti resistance to the deltamethrin insecticide in the populations investigated. The first Genetic Sexing Strain in Ae. albopictus for rapid mass sex separation built for Wolbachia-based sterile male control strategy was produced. Finally, we established the efficacy of specific innovative baited traps for capturing Ae. aegypti females.

Regarding social sciences, a database of articles, documents, and policies related to Zika scientific history in Brazil, focusing on epistemological and political controversies, was built, as well as a database of articles published about ZIKV in the French press in 2016. Zika outbreak repercussion were investigated in social media in Brazil, including fieldwork in pregnant women from Manaus-Amazonas. In addition, a survey was conducted in French Guiana about publicâ€™s beliefs, attitudes & behaviours in response to the ZIKV epidemic and the analysis of Zika spatial dynamics associated with territorial vulnerability is ongoing in Brazil.

Communication to the scientific community was ensured through the publication of more than 50 scientific articles, and dissemination to the public performed through press releases, website, twitter channel and an open access repository with ZIKAlliance articles.

In addition, a data harmonization meeting was organized with representatives of the 2 other EC-funded research projects on ZIKV, ZIKAction and ZIKAPlan. Protocols were harmonized and data management platforms of ZIKAlliance and ZIKAction shared. External quality assessment for molecular testing w

Final results

PW & CH cohorts will be key to (i) estimate the risk of abnormalities later in childhood, (ii) investigate co-factors/effect modifiers explaining the variability between current risk estimates, (iii) elucidate the differential risk between infection (mother, child) & congenital/infancy abnormality.
The project will evaluate diagnostic algorithms and reconcile data among local cohorts for pooled analysis. Assessment of innate responses and potential contribution to transmission to the fetus and subsequent brain damage will be produced.
The programme will further identify targets and candidates for antiviral therapy. Ongoing research uncovers pathogenesis mechanisms in cellular and animal models, including sexual and maternal-fetal transmission.
Environmental studies will show that ZIKV is less readily establishes sylvatic cycles than deemed upon modelling approaches and entomology studies will characterise vector competence of mosquitoes worldwide, co-infections with other arboviruses, mosquito immunity and new mosquito control tools.
Social sciences will produce an estimate burden of disability in ZIKV patients, a comprehensive analysis of health needs and an assessment of costs in affected families, public health sector and society to improve public health interventions and policies.
The harmonization efforts between the 3 EC-funded Zika research consortia will constitute an example of close scientific collaboration in the context of a Public Health Emergency of International Concern. The 3 consortia are building the skills of clinical and laboratory researchers at several sites across Latin America.