Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - ZikaPLAN (Zika Preparedness Latin American Network)
Teaser
The ZikaPLAN has 2 main objectives: (A) Addressing ZIKA - Tackling knowledge gaps and needs in key areas of interest to the current Zika Outbreak; (B) Prepare for beyond Zika - Building a sustainable Latin-American EID Preparedness and Response capacity. Although Zika...
Summary
The ZikaPLAN has 2 main objectives: (A) Addressing ZIKA - Tackling knowledge gaps and needs in key areas of interest to the current Zika Outbreak; (B) Prepare for beyond Zika - Building a sustainable Latin-American EID Preparedness and Response capacity. Although Zika incidence declined dramatically within a year of its emergence, all predictions indicate that it can return in 5-10 years or explode in other parts of the world. The project work plan is designed with these dual, complementary purposes, as planned activities, a few given here, primarily address Purpose A (A1-7), while contributing to Purpose B (B1-3).
A1. To determine the attack rate & full clinical spectrum of Congenital Zika Syndrome builds on the MERG (Microcephaly Epidemic Research Group) work as we have enrolled high number of patients regardless the decline in Zika incidence.
A2. For defining the spectrum of neurological diseases associated with Zika virus (ZIKV) infection, in the central nervous system (CNS) & peripheral nervous system (PNS) of adults & children (excluding neonates), we are conducting retrospective & prospective cohort studies of neurological Zika disease across Brazil & Colombia.
A3. Investigate the extent of & factors associated with sexual transmission of Zika in humans and animal models: we have established ‘testis model’ which can be employed in the future to evaluate the efficacy of potential drug candidates.
A4. Discover & characterise the mechanistic pathways of ZIKV infection in the pathogenesis of CNS and PNS injury: Zika virus tropism in the peripheral & central nervous systems have been performed in vitro.
A5. Develop and validate tools for the diagnosis, surveillance & research on ZIKV: a virtual bio bank for the evaluation of Zika diagnostic tests has been established.
A6. Identify the major T-cell epitopes & cross-reactive B-cell epitopes: more than 2,000 T cell epitopes identified, in vitro antibody dependent enhancement has been demonstrated.
A7. To assess the evolution of the ZIKV outbreak in Brazil more than 10,000 subjects have blood samples stored with ethics package in place. The most appropriate assay to determine recent or past ZIKV infection has been identified.
B1. Mathematical models to inform public health policies are underway in terms of predicting the evolution of Zika, and developing best vector control packages.
B2. Novel wash-in detergent formulations & long-lasting plastic technologies are under development, combined with qualitative research on community acceptance.
B3. The establishment of a Latin-American & Caribbean network: together with other consortia, ZIKAlliance & ZIKAction has led to REDe, a widely-used online platform for training resources.
Work performed
Since the initiation of ZikaPLAN we have successfully established two multicentric cohorts (WP1): a cohort of pregnant women with an episode of rash during pregnancy & a cohort of children with suspected prenatal exposure to ZIKV. In total, more than 1000 pregnant women with rash have been identified, of whom 208 tested positive for ZIKV by RT-PCR and 250 children with microcephaly & other clinical manifestations of Congenital Zika Syndrome are being followed up over the first three years of life.
WP2 has optimised molecular & serological diagnostic assays recruiting neurological patients from different sites in Brazil and Colombia. WP 3 established a ‘testis model’, which can be used to evaluate the efficacy of potential drug candidates. WP 4 is using various animal & in-vitro studies to differentiate autoimmune versus direct neuropathic phenomena of ZIKV.
WP5 has established a decentralized bio bank for the evaluation of Zika diagnostic tests, also resulting in harmonized bio-banking procedures. WP6 demonstrated Antibody-dependent enhancement (ADE) from a prior ZIKV infection followed by a dengue virus (DENV), identifying more than 2,000 T-cell epitope responses.
WP 8 is running a Phase III trial to test the efficacy of a dengue vaccine in 16 sites across Brazil, collecting baseline samples of 17000 participants. We are finalising creating a Latin American network for congenital anomaly surveillance (Rede Latino Americana de Malformaciones Congénitas (RELAMC) providing an online platform & database with ready-to-use tools..
In WP 9 a strategy-level mathematical model has been constructed, generating initial results for novel methods (Sterile Insect Technique, Release of Insects carrying dominant Lethal genes, Wolbachia). The Global Vector Hub (GVH) will establish a community of practice for the vector control community, including researchers, vector control experts & policy makers. WP10 is developing novel repellent-based control measures including studying the community acceptability of such technologies.
WP 11 launched REDe (an online platform) for knowledge sharing across the LAC countries. Qualitative research in Brazil on the perceptions of & reactions to Zika messaging conducted in WP12. The WP13 handled coordination activities for the consortium. All joint efforts of the 3 Zika consortia (WP14 & 15) on data sharing & harmonization and overall collaboration are functioning well.
Final results
For understanding Congenital Zika Syndrome, MERG has collected an unprecedented amount of long-term follow up data on Zika affected neonates including socioeconomic information, necessary to make a value proposition for Zika vaccine development. Following qualitative research in Brazil, actionable social messages are being developed for affected communities.
An International Committee for Birth Defect Surveillance and an Inventory of Birth Defect Surveillance Tools have been established. A new Tablet App is being tested for use in low resource settings.
The multi-centre clinical studies have led to various outcomes that can be exploited beyond ZIkaPLAN: (1) Utilisation of online platforms for data collection to build capacity for clinical research into neurological disease. (2) Established biobanks in Colombia and Brazil with ongoing sample collection. (3) Production of clinical management guidance on GBS. IGOS has adapted its protocols, made them widely available, and expanded its network. This will benefit Latin America beyond the immediate response to Zika.
Diagnostic evaluation platform work has resulted in harmonized bio-banking procedures, a manual & Standard Operating Procedures on sample collection & characterization to ensure harmonisation of bio-banking procedures. Requests by the industry & UNICEF for evaluating new tests are increasing.
Major B cell epitopes on ZIKV have been identified, both important for diagnostics and vaccine development. The large range of T-cell epitopes will be important for the industry in terms of ZIKV vaccine development. One of the major impacts of ZikaPLAN will be the longitudinal cohort study involving 17,000 subjects aged 2-60 years in 16 geographic locations in Brazil. Samples are now being analysed, and we will be able to assess the annual incidence, as well as age specific seroprevalence from these locations. Such information is important for policy-makers & vaccine developers.
REDe’s website is highly frequented. REDe is working in strong partnerships with organisations like Fiocruz, PAHO, public-private partnerships, well connected to international networks (GLoPID-R and PREPARE). ZikaPLAN members are sought-after speakers at international conferences and at WHO technical consultations.
Website & more info
More info: https://zikaplan.tghn.org.