Periodic Reporting for period 3 - ZikaPLAN (Zika Preparedness Latin American Network)
Reporting period: 2019-10-01 to 2021-03-31
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 was implemented with these dual complementary purposes, as planned activities, significant ones include Purpose A (A1-7), contributing to Purpose B (B1-3).
A1. To determine the attack rate & full clinical spectrum of Congenital Zika Syndrome: built on the MERG (Microcephaly Epidemic Research Group) work with enrolment of 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): conducted 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: 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 was 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 is functional.
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 was demonstrated.
A7. To assess the evolution of the ZIKV outbreak in Brazil from more than 16,000 blood samples with ethics in place: most appropriate assay to determine recent or past ZIKV infection developed, intial analysis conducted.
B1. Mathematical models to inform public health policies in terms of predicting the evolution of Zika, & developing best vector control packages were developed.
B2. Novel wash-in detergent formulations & long-lasting plastic technologies were explored and combined with qualitative research on community acceptance.
B3. The establishment of a Latin-American & Caribbean network: together with other consortia, ZIKAlliance & ZIKAction: REDe - a widely-used online platform for training resources created.
A1. To determine the attack rate & full clinical spectrum of Congenital Zika Syndrome: built on the MERG (Microcephaly Epidemic Research Group) work with enrolment of 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): conducted 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: 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 was 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 is functional.
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 was demonstrated.
A7. To assess the evolution of the ZIKV outbreak in Brazil from more than 16,000 blood samples with ethics in place: most appropriate assay to determine recent or past ZIKV infection developed, intial analysis conducted.
B1. Mathematical models to inform public health policies in terms of predicting the evolution of Zika, & developing best vector control packages were developed.
B2. Novel wash-in detergent formulations & long-lasting plastic technologies were explored and combined with qualitative research on community acceptance.
B3. The establishment of a Latin-American & Caribbean network: together with other consortia, ZIKAlliance & ZIKAction: REDe - a widely-used online platform for training resources created.
ZikaPLAN WP1 investigations yielded some of the most robust estimates of the absolute risks associated with congenital Zika virus infections and provided unique insights regarding the prognosis and health needs of children born with Congenital Zika Syndrome (CZS). It directly informed the case definition of CZS used by the public health authorities in Brazil. WP2 work led to improved arbovirus diagnostic testing, enhanced clinical understanding of Zika neurological disease, & to development of research preparedness in all partner-countries. Zika-associated neurological disease in adult & paediatric patients were characterized & provided evidence that risk of stroke may be increased in patients who have infection with more than one arbovirus (e.g. ZIKV & chikungunya), which has significant implications in endemic areas.
The WP3 studies indicate a high epidemic potential for the African ZIKV strains, which could pose a serious public health threat. WP 4 used various animal & in-vitro studies to differentiate autoimmune versus direct neuropathic phenomena of ZIKV. WP5 developed new Zika diagnostic tests (antibody and NAT) & tools for the diagnosis, surveillance & research on ZIKV & has established a bio bank and network of sites for the validation & evaluation of Zika diagnostic tests. WPs 6 & 7 inform about the phylogenetic analyses & identified a potential explanation why ZIKV emerged explosively in the Americas & not in Asia.
In the WP8, a Latin American network for congenital anomaly surveillance (Rede Latino Americana de Malformaciones Congénitas (ReLAMC) has been formed. A Mobile App for birth defect surveillance is currently being adopted in various LMICs. The Global Vector Hub (GVH) is functioning as the ‘community of practice’ for the vector control. The final results of the Brazilian Butantan study (analysis based on 16,235 subjects from WP8), in WP9, will feed relevant information for the development of models to help policy makers & vaccine developers. WP10 used social science methods & mathematical modelling to characterize the target product profile of wash-in detergent formulation and impregnated clothing products.
WP11 maintained REDe,the online scientific network for knowledge sharing across the LAC countries, other LMICs & has built many regional sites. Communication & dissemination & exploitation of achievements was facilitated in WP12. The WP13 managed this international cooperation with genuine coordination. All joint efforts of the 3 EU-Zika consortia (WP14 & 15) on data sharing & harmonization & joint efforts set an example of ‘successful collaboration’ among 3 large transnational consortia.
The WP3 studies indicate a high epidemic potential for the African ZIKV strains, which could pose a serious public health threat. WP 4 used various animal & in-vitro studies to differentiate autoimmune versus direct neuropathic phenomena of ZIKV. WP5 developed new Zika diagnostic tests (antibody and NAT) & tools for the diagnosis, surveillance & research on ZIKV & has established a bio bank and network of sites for the validation & evaluation of Zika diagnostic tests. WPs 6 & 7 inform about the phylogenetic analyses & identified a potential explanation why ZIKV emerged explosively in the Americas & not in Asia.
In the WP8, a Latin American network for congenital anomaly surveillance (Rede Latino Americana de Malformaciones Congénitas (ReLAMC) has been formed. A Mobile App for birth defect surveillance is currently being adopted in various LMICs. The Global Vector Hub (GVH) is functioning as the ‘community of practice’ for the vector control. The final results of the Brazilian Butantan study (analysis based on 16,235 subjects from WP8), in WP9, will feed relevant information for the development of models to help policy makers & vaccine developers. WP10 used social science methods & mathematical modelling to characterize the target product profile of wash-in detergent formulation and impregnated clothing products.
WP11 maintained REDe,the online scientific network for knowledge sharing across the LAC countries, other LMICs & has built many regional sites. Communication & dissemination & exploitation of achievements was facilitated in WP12. The WP13 managed this international cooperation with genuine coordination. All joint efforts of the 3 EU-Zika consortia (WP14 & 15) on data sharing & harmonization & joint efforts set an example of ‘successful collaboration’ among 3 large transnational consortia.
For describing the full spectrum Congenital Zika Syndrome, the MERG group has unprecedented amount of long-term follow up data on Zika affected neonates including socioeconomic information which will go beyond ZikaPLAN. An International Committee for Birth Defect Surveillance & an Inventory of Birth Defect Surveillance Tools is established and available for further use. A Tablet App is available for use and adopted in many low resource settings.
The multi-centre clinical studies have led to various outcomes that will 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. This will benefit Latin America beyond the ZikaPLAN project.
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 addressed.
Major T & B cell epitopes on ZIKV were identified, both important for diagnostics and vaccine development. One of the major impacts of ZikaPLAN will be the longitudinal cohort study involving 16,235 subjects aged 2-59 years in 16 geographic locations in Brazil. Samples are now being analysed to assess seroprevalence by age, gender & geographic location. Such information is necessary for policy-makers & vaccine developers.
REDe website is highly frequented. REDe works in strong partnerships with organisations like Fiocruz, PAHO, public-private partnerships, well connected to international networks (GLoPID-R, ALERRT, 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 and collaboration.
The multi-centre clinical studies have led to various outcomes that will 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. This will benefit Latin America beyond the ZikaPLAN project.
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 addressed.
Major T & B cell epitopes on ZIKV were identified, both important for diagnostics and vaccine development. One of the major impacts of ZikaPLAN will be the longitudinal cohort study involving 16,235 subjects aged 2-59 years in 16 geographic locations in Brazil. Samples are now being analysed to assess seroprevalence by age, gender & geographic location. Such information is necessary for policy-makers & vaccine developers.
REDe website is highly frequented. REDe works in strong partnerships with organisations like Fiocruz, PAHO, public-private partnerships, well connected to international networks (GLoPID-R, ALERRT, 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 and collaboration.