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Zika Preparedness Latin American Network

Periodic Reporting for period 2 - ZikaPLAN (Zika Preparedness Latin American Network)

Reporting period: 2018-04-01 to 2019-09-30

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, which is now a widely used online platform for training resources.
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 380 children with microcephaly & other clinical manifestations of Congenital Zika Syndrome are being followed up over the first three years of life.
WP2 has expanded its network of neurologists across Colombia and Brazil & conducted various case control studies. WP3 established a ‘testis model’, which is in use to evaluate the efficacy of potential drug candidates. WP4 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 conducted phylogenetic analyses & identified a potential explanation why ZIKV emerged explosively in the Americas and not in Asia. Antibody-dependent enhancement (ADE) from a prior ZIKV infection followed by a dengue virus (DENV), identifying more than 2,000 T-cell epitope responses.
WP8 has completed the collection of baseline samples of 16000 participants, and evaluated the most sensitive and specific assay to determine past ZIKV infection. A Latin American network for congenital anomaly surveillance (Rede Latino Americana de Malformaciones Congénitas (RELAMC) was formed. A Tablet App for birth defect surveillance is completed and currently being field-tested for its usefulness. The Global Vector Hub (GVH) is maintaining the community of practice for the vector control community.
In WP9, 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). WP10 is developing novel repellent-based control measures and completed focus group discussions in Brazil and Colombia on community acceptability of such technologies.
WP11 continues to maintain REDe (an online platform) for knowledge sharing across the LAC countries and has built many regional sites. Qualitative research in Brazil on the perceptions of & reactions to Zika messaging was concluded in WP12. The WP13 is leading this international cooperation with genuine coordination. All joint efforts of the 3 Zika consortia (WP14 & 15) on data sharing & harmonization and overall collaboration are progressing well.
For describing the full spectrum Congenital Zika Syndrome, MERG has unprecedented amount of long-term follow up data on Zika affected neonates including socioeconomic information. An International Committee for Birth Defect Surveillance and an Inventory of Birth Defect Surveillance Tools have been established and are available for further use. A new Tablet App is fully developed and is being field-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 courses and an expert consensus publication in a high profile journal on clinical management guidance on GBS. IGOS has adapted its protocols, made them widely available, and expanded its network by establishing IGOS-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 T and B cell epitopes on ZIKV have been identified, both important for diagnostics and vaccine development. One of the major impacts of ZikaPLAN will be the longitudinal cohort study involving 17,000 subjects aged 2-59 years in 16 geographic locations in Brazil. Samples are now being analysed, and we will be able to assess seroprevalence by age, gender and geographic location. Such information is important for policy-makers & vaccine developers.

REDe website is highly frequented. REDe is working in partnerships with organisations like Fiocruz, PAHO and well connected to international networks (GLoPID-R, PREPARE, ISARIC). Our members are sought-after speakers at international conferences and at WHO technical consultations. EU DG-RTD has recognised ZikaPLAN as an outstanding example of successful international cooperation.
Consortia meeting Cuba
Press release uptake
Power point template
Twitter screenshot
Poster of the project
Group photo of Consortium Meeting at Cali, Colombia 2019 for RP2
News article in Spanish in Colombia newspaper 2019 for RP2
Kick-Off meeting photos