UK-Brazil Joint Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE)

Lead Research Organisation: University of Oxford
Department Name: Zoology

Abstract

Recently, Brazil has been affected by unexpected and explosive epidemics of insect-transmitted viruses (arboviruses), most notably Zika, chikungunya, dengue, and yellow fever viruses. The huge economic burden of the Zika epidemic in Brazil and the widespread presence of urban mosquitos in the country highlight an urgent need for accurate predictions of disease spread, particularly in large, densely populated regions. Our UK-Brazil Partnership (CADDE) will enhance and expand an excellent existing collaborations, with the aim of anticipating and controlling future epidemics of arboviruses in Brazil. It is our vision for CADDE to become a strategic centre of excellence for research in South America that focuses on providing timely analysis, based on genomic, epidemiological and geographic evidence, to anticipate and control transmission of arboviruses, today and in the future..

Our research questions include: 1) What arboviruses circulate in human, mosquito and reservoir populations in Brazil? 2) Where and how do arboviruses persist during non-epidemic periods? 3) What are the biological and medical implications of the genetic diversity of circulating arboviruses and of mutations in their genomes? 4) What factors control the transformation of a single introduction of a new arbovirus into human populations into sizeable epidemic, and 5) how quickly can we detect and characterise such epidemics, and how best to respond? Active virus surveillance in vectors and reservoirs will be combined with seroprevalence surveys in blood donors (to characterise features such as virus genomics, transmission, and immunity). Novel portable genome sequencing technologies and modern real-time epidemiological analyses will be applied to the most important arboviruses in Brazil.

Using modern techniques that can unify the information from genomics and epidemiology, CADDE will strengthen the evidence base for public health actions, and strengthen the capacity of Brazilian health system to respond to emerging arboviral diseases. We will transform local capacity by training research scientists and public health personnel in field epidemiology, laboratory testing, the use of portable genomic technologies, and computational and statistical methods.

Technical Summary

1. What is the genetic diversity of Brazilian arboviruses?
We will develop rapid cost-effective sequencing protocols (specific & untargeted) for Brazilian arboviruses and apply them to human, vector & animal samples from 5 established cohorts. We will test hypotheses of associations between arbovirus genetic diversity and key phenotypes, e.g. (1) Are there viral mutations linked to Zika-associated microcephaly cases? (2) What is the epidemiological impact of ZIKV sexual transmission? (3) Are there viral genomic signatures of sylvatic vs urban YFV transmission cycles? (4) Are there genomic signatures associated with disease severity or vector specificity for Brazilian arboviruses?
2. Why do arbovirus epidemics spread & persist?
To better understand local arbovirus transmission in São Paulo and how this relates to wider virus spread , we will investigate factors driving the spread and persistence of transmission in vector, human and non-human primate populations. We will determine when and where is transmission risk for arbovirus infection is highest, and whether risk zones vary under different scenarios.
3. Can we quantify mobility and anticipate transmission?
Prevention and control measures are hindered by poor understanding of how human, vector and reservoir species mobility contributes to arbovirus spatial spread. Through geospatial modelling we will identify hotspots of transmission in São Paulo and Brazil, with the aim of anticipating arbovirus dissemination. We will develop a platform for real-time arbovirus detection and epidemiological analysis.
4. How do we develop a precision public health model for Brazil?
We propose that precise public health inventions are possible through the integration of data from multiple data sources. Specifically we will combine primary surveillance data with rapid analysis systems to track and predict disease distributions. Crucially we will develop Brazilian technical expertise and capacity to act upon this information.

Planned Impact

The Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) will enhance the ability of the Brazilian health system to prepare for and to respond to future outbreaks of arboviruses. We will improve the integration of cutting-edge genomic, bioinformatics and epidemiological approaches within existing public health systems in Brazil. We will develop and apply new techniques to collect and integrate genomic and epidemiological data in order to better understand viral transmission. Basing public health policy and response on scientific data analysis will allow response to new outbreaks to be deployed more rapidly and more efficiently by local and national public health bodies across São Paulo and Brazil.

We will share the data that we generate within Brazil in an open-access manner with international public health agencies, including WHO and PAHO. The early identification of newly emerging arboviral pathogens in humans via metagenomic protocols will allow rapid development of standardized assays for high-throughput surveillance that can be adopted cross-continentally by WHO and PAHO. Additionally, CADDE will improve the global understanding of the epidemiology of emerging and existing arboviral pathogens. We will quantify risk-factors for arboviral transmission hotspots that can be translated to international scales, and also provide estimates of the prevalence of asymptomatic infections. This knowledge is will help guide the WHO and PAHO to make effective policy to protect public health, including the evaluation of vaccination targets.

We will improve the capacity of laboratories in Brazil to generate and access genomic and epidemiological data through a detailed training programme and development of simple platforms to display epidemiological data in real-time. By developing simple, free-to-use platforms that automatically display real-time analyses of collated epidemiological data to local public health personnel, we will maximise te use of scientific data in public health response. We will provide training in basic epidemiological and computation analyses to public health personnel in São Paulo, empowering them to perform additional analyses and allow a flexible and localised response to new outbreaks. We will introduce public health laboratories in Brazil to novel, portable genomic technologies, allowing local laboratories to generate critically important sequence data within 24 hours of sample collection. The widespread adoption of rapid sequencing technologies across Brazil will allow hypotheses about the transmission of arboviruses to be tested in real-time with genomic data, and enable genomic data to directly guide the design of local public health interventions.

The wider scientific community will benefit from the data generated by CADDE. All data, methods and results that will be generated during this project will be made available in an open-access manner, allowing the highest possible impact of our work. Techniques that are developed through CADDE will drive further research into integrated epidemiological and genomic analyses that can be deployed in real-time to help control viral transmission.

The general public in São Paulo and across Brazil will benefit from improved public healthcare as a result of the use of new technologies to improve outbreak responsiveness. We hope that the general public will gain a better understanding of arboviral transmission and modern sequencing technologies through the provision of regular media interviews by members of the CADDE team about our ongoing work, and opportunities to discuss directly with scientists at dedicated public engagement events.
 
Title Aedes aegypti illustration by designer Paulo Presti 
Description Artwork for CADDE website 
Type Of Art Artwork 
Year Produced 2019 
Impact The illustration has attracted considerable attention to our website and helped to increase awareness of mosquito surveillance and taxonomy in Brazil. 
URL https://www.caddecentre.org/arbovirology/
 
Description Our work to date has dramatically improved the availability of yellow fever virus (YFV), dengue virus and chikungunya virus (CHIKV) genome sequences in Brazil. We are using these genomes to generate new epidemiological findings about viral spread (CADDE Deliverable 9). In total, we have sequenced over 500 new genomes of yellow fever virus over the last year, which we now include as an important new public resource on our project website (https://www.caddecentre.org/genomics/). We have finalized a study on the spatial spread of yellow fever virus in São Paulo state using a subset of these genomes, which changes our understanding of how the virus was introduced into urban regions of São Paulo state. We are currently conducting analyses that will pinpoint the drivers of infection between different areas at a larger scale in southeast Brazil.

We are working to explore the clinical impact of multiple arboviruses, including CHIKV and ZIKV. Specifically, we have recently submitted a report that shows that CHIKV-ECSA strains can cause death in individuals from both risk and non-risk groups, including young adults. We have sequenced 7 new genomes of ZIKV from infants with microcephaly, and have identified that there are no shared viral variants that could specifically explain the occurrence of microcephaly (https://cadde.herokuapp.com/ZIKV).

We have validated a new protocol to amplify and sequence up to 8 arboviral genomes using the same protocol (Deliverable 1). We have also fully developed a new metaviromic sequencing method for the Oxford Nanopore Minion (Deliverable 3 and 4), and published these protocols freely on our website (Deliverable 14) This rapid protocol can be deployed to discover and flexibly sequence many different virus genomes from clinical cases with unknown etiology. We have used this protocol to investigate patients suspected of YFV infection who tested negative for YFV. Using these techniques, we identified a new strain of Sabia virus (an arenavirus that can cause hemorrhagic fever) in Brazil. This finding has led us to question what proportion of YFV-suspected patients for which YFV could not be confirmed died from other causes. We will follow this new research direction in the coming months.

Working closely with the Ministry of Health, we have sequenced viral genomes from the first 2 SARS-CoV-2 infections in Brazil (the first also in South America). Our results have been important to show that both cases were more closely phylogenetically linked to cases outside of Brazil than to each other. When combined with the patient travel information, this indicates that the two confirmed cases in Brazil are likely the result of separate introductions to the country rather than the localized spread in Brazil. Analyses of SARS-CoV-2 are a new research direction for the project but are extremely important given the anticipated health impact of this new outbreak.

We have led a practical workshop on genomic sequencing and analysis methodologies for approximately 30 participants from across the globe, and have trained 7 people from laboratories at the Brazilian Ministry of Health. Several of these researchers are currently using genomic techniques to sequence cases of SARS-CoV-2 in their own countries.

Through these activities, we have established 6 new research collaborations (detailed elsewhere). Of note, we are now working with the Ministry of Health of Brazil. We benefit from data shared by them and help to support their activities detecting and analyzing the spread of viral disease.
Exploitation Route CADDE is strengthening the scientific evidence base for public health in Brazil, enhancing the capacity of the Brazilian research and health systems, and is preparing for, and responding to, current and future outbreaks of emerging and re-emerging arboviruses. Our discovery of hidden deadly hemorrhagic fever infections in Sao Paulo that were previously attributed to yellow fever and the rapid development of new tools to identify its transmission is an example of the project's commitment to provide key information for public health response in real-time.

CADDE is strengthening collaborative links between public health researchers, clinical virologists and world leaders in genomics, virus evolution and genomic epidemiology. Moreover, are will develop epidemiological, mathematical, spatial and genomic approaches to quantify arboviral transmission and inform disease control at fine spatial scales. Knowledge and expertise will continue to be transferred through capacity-building and technology-transfer initiatives, with the aim of improving the preparedness of the Brazilian health system to future arboviral disease outbreaks. This will be relevant for any pathogen threat. As an example of CADDE's flexibility, our project has recently generated the first genome and corresponding phylogenetic analysis of the first COVID-19 in South America in a record time of 48 hours. CADDE will also continue to build on our existing communication corridors with policymakers (at WHO, PAHO and Brazilian Ministry of Health) to communicate our findings and maximize their societal impact.
Sectors Communities and Social Services/Policy,Education,Environment,Healthcare,Government, Democracy and Justice

URL https://www.caddecentre.org/
 
Description This is a free-text section that allows you to explain in more detail the economic and societal impact of the grant that you are reporting on. RCUK defines economic and societal impact as 'the demonstrable contribution that excellent research makes to society and the economy'. Economic and societal impacts embrace all the extremely diverse ways in which research-related knowledge and skills benefit individuals, organisations and nations by: Our findings have had broad impact both on health policy and on wider society. We have developed good links with the World Health Organisation (WHO), the Pan American Health Organisation (PAHO) and Brazilian Ministry of Health that are allowing project findings to directly impact on governmental and regional health policy. All of our research findings to date have been directly communicated with the Brazilian Ministry of Health, including the finding that arenavirus has recent caused cases of haemorrhagic fever in Brazil. The leading PI of CADDE, Prof Nuno Faria, has been invited to be a member of WHO's Global Laboratory Alliance for the Detection of High-Threat Pathogens (GLAD-HP), and is currently participating in weekly update meetings on the spread of SARS-Cov-2. He facilitates knowledge transfer from the WHO directly to PAHO, the Brazilian Ministry of Health and CADDE team members. Prof Faria is also in communication via WhatsApp with the Secretary of Health Surveillance at the Brazilian Ministry of Health, and is helping to provide consultancy during the current outbreak. Our findings on SARS-CoV-2 have directly impacted preparedness by the Brazilian government. Our genomic sequencing is being used to support epidemiological studies that investigate the extent to which SARS-CoV-2 is being spread in Brazil via repeated introductions vs local transmission, each of which would demand different control measures. In addition, using air travel information, we showed that >70% of flights from countries with COVID-19 cases would arrive in São Paulo. The government has currently concentrated genomic sequencing capacity in laboratories in São Paulo in response to this finding. In addition to impact within Brazil, we have helped improve preparedness and genomic sequencing capacity in other laboratories across South America and more widely. CADDE directly trained 30 participants in portable MinION sequencing during a workshop in December 2019. Several participants are now using the techniques to sequence arboviruses and emerging viruses such as SARS-CoV-2 in their own countries, including in Ministry of Health laboratories. We continue to support their activities, through openly sharing expertise and shipping limited specific reagents (e.g., primers for sequencing of SARS-CoV-2) to Ministry of Health laboratories including those in Panama, Mexico, Angola and Portugal. We have actively engaged with journalists to share our activities with a wider audience. So far, our activities have been featured in >500 published articles, we have given >20 TV interviews, and our recent work on SARS-CoV-2 has been captured by the famous Brazilian cartoonist Mauricio Sousa. Many of these articles feature the key role of the women in our collaboration in the work, thereby driving the agenda of supporting women in STEM to a wider audience. We hope that this will inspire an increasingly diverse segment of society to enter careers in science, or engage with scientific findings.
First Year Of Impact 2019
Sector Communities and Social Services/Policy,Education,Environment,Healthcare,Government, Democracy and Justice,Culture, Heritage, Museums and Collections
Impact Types Cultural,Societal,Economic,Policy & public services

 
Description CADDE Website and Twitter
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact The CADDE website (https://www.caddecentre.org/) reached 3849 new users in its first 3 months (Google Analytics). We had a total of 4,504 sessions and 7,617 page views. Most of its audience is Brazilian (77%) and we are currently translating the website to Portuguese and Spanish so we can further increase CADDE's visibility throughout Latin America. Regarding our Twitter Account, @CaddeProject has already 865 followers (as of 12 March 2020). Since the beginning of the @CaddeProject account, we have had 253,481 Tweet Impressions (number of times a tweet shows up in a person's timeline). Both the website and the Twitter analytics attest to the significant impact that CADDE is having in the scientific community by influencing research and improving knowledge in the field of emergent infectious diseases.
URL https://www.caddecentre.org/
 
Description Consultancy to SVS Ministry of Health on COVID19 Surveillance
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Upon the first detection of COVID19 in Brazil (26 Feb 2020), PI Nuno Faria provided upon request information to the SVS Ministry of Health in how to proceed. One major limitation of rapid and equitable access to diagnostic was the lack of positive control for COVID laboratory screening. Following our suggestions, SVS requested a local laboratory to amplify the virus which was then inactivated and distributed across the network of public health laboratories in Brazil.
 
Description First CADDE workshop on Genomic Epidemiology
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact The CADDE Genomic Epidemiology Workshop (2 to 6 December 2019) was a training hands-on course based on integrating Oxford Nanopore MinION sequencing with genetic data analysis for outbreak investigation. Researchers were trained in library preparation, running the MinION sequencer, and analyzing sequencing data using bioinformatics and phylogenetic tools. Using novel protocols developed by the CADDE project, researchers generated dengue virus genomes in only a few hours. The workshop trained 16 researchers across different regions in Brazil and 18 other researchers from 16 different countries, including from 7 Ministry of Health laboratories: Brazil, Puerto Rico, Panama, Mexico, Colombia, Angola, and Portugal. Three months after our workshop, 6 of these laboratories are using methods learnt during our CADDE workshop to sequence SARS-CoV-2 genomes cases from the new outbreak that will be key to monitor the efficacy of current diagnostic tools, design vaccines and track the international spread of the virus.
URL https://www.caddecentre.org/programme-for-the-cadde-genomic-epidemiology-workshop/
 
Description Global Laboratories Alliance for the Diagnosis of High Threat Pathogens
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact World Health Organization (WHO) headquarters coordinate the Global Laboratories Alliance for the Diagnosis of High Threat Pathogens (GLAD HP). CADDE PI Prof Faria has been invited to the GLAD HP alliance as an expert in genetic analyses and data sharing in November 2019. As a result of his involvement in GLAD HP, CADDE has been able to capitalize on rapid knowledge and international capacity from weekly GLAD HP TC calls sharing important information concerning laboratory testing and the dynamics of COVID-19.
 
Description Leading International Guidelines for COVID19 sequencing (WHO) (ongoing)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description A translational study for the identification, characterisation and validation of severity biomarkers in arbovirus infections
Amount R$ 4,000,000 (BRL)
Organisation São Paulo Research Foundation (FAPESP) 
Sector Public
Country Brazil
Start 12/2017 
End 12/2021
 
Description An actionable framework for surveillance of mosquito-borne viral diseases in Mexico - QMUL Global Challenge Research Fund, Large Grant Scheme 2019-20
Amount £20,000 (GBP)
Organisation Queen Mary University of London 
Sector Academic/University
Country United Kingdom
Start 12/2020 
End 12/2021
 
Title Metagenomics protocol for laboratory diagnostic 
Description We report a Smart-Seq (Switch Mechanism at the 5' End of RNA Templates) protocol using random 9-n priming. The protocol is compatible with the Oxford Nanopore Technologies RLB rapid, barcoded adapters available from the SQK-RPB004 kit. This protocol has been developed and tested by the CADDE team and has been used to successfully identify Sabia virus infections in yellow fever suspected cases. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact The method was able to successfully identify a virus that hadn't been detected since 1990 (see our Publication List). Our results suggested that several yellow fever suspected cases that tested negative by PCR may have been caused by Sabia virus, an arenavirus that causes hemorrhagic fever. 
URL https://www.caddecentre.org/protocols/
 
Title Real-time genetic analysis of arboviruses in Brazil 
Description We designed a CADDE auspice-nextstrain platform to have real-time visualizations of yellow fever, chikungunya, dengue, and oropouche virus phylogenies and correspondent diversity along virus genomes. 
Type Of Material Improvements to research infrastructure 
Year Produced 2020 
Provided To Others? Yes  
Impact The tool has been used by the Secretary of Health in Sao Paulo, with the Ministry of Health and the Pan American Health Organization to detect spread into new regions and changes in arbovirus genomes. 
URL https://www.caddecentre.org/genomics/
 
Title Datasets of genome sequences from arboviruses 
Description Our research database includes updated visualizations of genomic data generated by CADDE and other groups for improved epidemiological understanding and outbreak response in Brazil. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact The database has been used by Pan American Health Organization and the Brazilian Ministry of Health. Five publications are currently being prepared to describe in detail the >800 genome sequences (>500 yellow fever virus, 200 dengue, 100 chikungunya ) generated over the first year of the project. 
URL https://www.caddecentre.org/genomics/
 
Title Dengue Sao Paulo database 
Description The database is composed of dengue notified cases that were extracted from the Health Surveillance System database. Notification of every suspect dengue case is mandatory, and dengue surveillance is considered a priority in the epidemiological surveillance system in Brazil. About 50% of cases were reported within 3 days after the first symptoms, and 90% of cases were digitized within 7 days of notification. A suspect dengue case is defined as any person presenting with acute fever and at least two of the following symptoms: nausea, vomiting, rash, myalgia, headache, retro-orbital pain, petechiae, positive loop test or leukopenia. The database encompasses information on age, gender, home address, clinical symptoms, specific laboratory investigation, probable site of dengue infection, name of health facility notifying the case (assumed to also be the location of treatment), disease severity and outcome. After notification from health professionals, the epidemiological surveillance department collects information and inputs the data into the digital database. At the central level, the database is post-processed: duplicate records are deleted, and medical and laboratory records are requested when needed for completeness of data. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact To the best of our knowledge, the database is the largest of its kind in the Americas. It will inform decision making in dengue control in Sao Paulo and Brazil. 
 
Title Field Survey Entomological Zones 
Description the largest concentration of fragments and continuous areas of the Atlantic forest in São Paulo State follows the coastline. Aiming to find genetically and statistically significant sampling zones for YFV, we conducted surveys in three forest areas, two of which are more than 150 km to north and south of the São Paulo city and a forested area adjacent to the metropolitan zone: A) Survey zone in São Paulo State (SPS) south coast - presenting the largest remaining area of preserved and original Atlantic Forest in Brazil. Several locations are being sampled in this area, especially in the cities: Itapitangui, Cananéia, and Pariquera-Açu; B) Survey zone in Cantareira Mountain Range in the north of São Paulo City (SPC) - areas with large amounts of parks, vegetated fragments and forest reserves very adjacent to the metropolitan zone of SPC. This zone covers sampling locations of different cities, notably: Caieiras, Diadema, São Paulo, Mairiporã; C) Survey zone in SPS north coast - presenting important Atlantic Forest coastline reserves with several quilombo settlements (high human presence integrated with forests), with primary and secondary forests. This sampling zone covers several localities surrounding Ubatuba city: Enseada, Itaguá, Perequê-Açu, and Barra Seca. 
Type Of Material Data handling & control 
Year Produced 2020 
Provided To Others? No  
Impact Data is currently being generated and as such, no impact has been achieved so far. 
 
Title Mosquito species database from Sao Paulo 
Description Our current mosquto database comprises the geographical extension of the entire State of São Paulo and adjacent areas from neighboring brazilian states. The current database has a total of 16266 records of specimens from the Culicidae family, and this amount is composed of records of 31 different genus and 239 different species. The database was collated from five different sources: (1) SpeciesLink biodiversity database, contributing with 6456 records, (2) Global Biodiversity Information Facility - GBIF adding more 224 records; (3) The global compendium of Aedes aegypti and Ae. albopictus occurrence from Kraemer and collaborators (2015), providing 2551 records, (4) 7035 records from São Paulo State Superintendence for Control of Endemic Diseases - SUCEN from collaborators Juliana Nogueira, Rosa Maria Tubaki, Gerson Laurindo Barbosa, Luis Filipe Mucci and Antonio Henrique Alves Gomes. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact The complete database was finalized in February 2020 and is currently being analyzed. 
 
Title Yellow fever human database (2014-2019) 
Description This is the largest yellow fever database of human cases available from the Americas. From 2016-2019 alone it contains 1959 confirmed cases in humans with detailed information. This data was obtained through our collaborator in FUNED Minas Gerais, Ministry of Health. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact The data was received in early March 2020. A publication and a Scientific Data paper will be prepared to share this data as soon as possible. 
 
Description Federal University of Rio de Janeiro 
Organisation Federal University of Rio de Janeiro
Country Brazil 
Sector Academic/University 
PI Contribution Our CADDE project has provided expertise and intellectual input in several genomic and phylodynamic projects from Renato Aguiar's team members. Given the role of human mobility in arbovirus spread, the partnership with the Federal University of Rio de Janeiro (Prof Renato Aguiar) will bring critical insight as it allow us to put our findings from Sao Paulo into a larger geographic context.
Collaborator Contribution Prof. Renato Aguiar (Federal University of Rio de Janeiro) has provided access to unique data - 7 genomes of Zika microcephaly samples (from 2015 to 2020 only 4 genomes have been made available). This data is directly relevant to test the association between Zika virus mutations and microcephaly status, the main goal of Deliverable 5. A visualization of the new Zika virus-associated microcephaly genomes being analyzed by the CADDE project together with Prof. Renato Aguiar can be visualized here: https://cadde.herokuapp.com/ZIKV?c=Microcephaly.
Impact This partnership will help to successfully complete Deliverable 5, and will help to put into context any genomic findings from data collected in Sao Paulo.
Start Year 2019
 
Description Instituto Evandro Chagas 
Organisation Evandro Chagas Institute
Country Brazil 
Sector Charity/Non Profit 
PI Contribution Our CADDE project has provided formal expertise in genomic sequencing to the Evandro Chagas Institute (IEC), one of the three reference laboratories in Brazil, through our first genomic epidemiology workshop entitled "CADDE Genomic Epidemiology Workshop" (Program here: https://www.caddecentre.org/programme-for-the-cadde-genomic-epidemiology-workshop/). Two members from IEC participated in the workshop where CADDE provided expertise in genomic sequencing using the latest technologies.
Collaborator Contribution IEC (Prof Marcio Nunes) has contributed with >150 yellow fever genomes from non-human primates and humans that are currently being analyzed to address key deliverables. The collaboration between CADDE and IEC has been very fruitful, and we have now gathered a total of >600 new yellow fever virus genomes from the recent outbreak. The novel genomic data will allow us to quantify arboviral transmission and inform arbovirus disease control (deliverables 7 and 8). A visualization of the yellow fever virus complete genome data that has been generated by the CADDE team can be found here: https://cadde.herokuapp.com/YFV.
Impact The collaboration with IEC reference laboratory has resulted in access to additional yellow fever data from the north of Brazil. This will be critical to the successful completion of key deliverables in our project. The partnership with IEC has the potential opens doors to future important collaborative links in arbovirus research.
Start Year 2019
 
Description Oswaldo Cruz Foundation 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Country Brazil 
Sector Public 
PI Contribution Our CADDE project has provided formal expertise in genomic sequencing to the Oswaldo Cruz Foundation through our first genomic epidemiology workshop entitled "CADDE Genomic Epidemiology Workshop" (Program here: https://www.caddecentre.org/programme-for-the-cadde-genomic-epidemiology-workshop/). Three members from Fiocruz participated in the workshop where CADDE provided expertise in genomic sequencing using the latest technologies.
Collaborator Contribution Oswaldo Cruz Foundation (Prof Ana Bispo) has contributed with 200 yellow fever positive from non-human primates and humans that are currently being analyzed to address key deliverables. The collaboration between CADDE and FioCruz has been very fruitful and we have now gathered >600 new yellow fever virus genomes from the recent outbreak. The novel genomic data will allow us to quantify arboviral transmission and inform arbovirus disease control (deliverables 7 and 8). A visualization of the yellow fever virus complete genome data that has been generated by the CADDE team can be found here: https://cadde.herokuapp.com/YFV.
Impact The collaboration with FioCruz has resulted in knowledge transfer and has helped facilitated the exchange of material between the CADDE team in Sao Paulo and FioCruz in Rio de Janeiro. It has contributed to a better understanding of the yellow fever virus epidemiology during the recent outbreak in the southeast region.
Start Year 2019
 
Description Secretaria de Vigilância em Saúde - Ministério da Saúde 
Organisation Government of Brazil
Country Brazil 
Sector Public 
PI Contribution Our CADDE project has provided formal expertise in genomics to the Ministry of Health team during our CADDE through our first genomic epidemiology workshop entitled "CADDE Genomic Epidemiology Workshop" (Program here: https://www.caddecentre.org/programme-for-the-cadde-genomic-epidemiology-workshop/). One member of the Ministry of Health was invited as a keynote speaker and continued as a participant for the one week course in genomic sequencing using the latest technologies.
Collaborator Contribution The strategic partnership with the Brazilian Ministério da Saúde (Dr. Wanderson de Oliveira and Dr. Julio Croda) (May 2019) started in August 2019 (https://twitter.com/CaddeProject/status/1161711565869072384) and has provided national-level arbovirus data that be important for real-time cartographies of arbovirus transmission (deliverable 10). It will also be key to promote the rapid-response outbreak protocols (deliverable 14). Moreover, this partnership further augments CADDE's collaboration network and is providing important information to guide policy at a national level.
Impact The collaboration with the Brazilian Ministry of Health is of utmost importance for CADDE and will be important to the successful completion of key deliverables in our project. Moreover, the partnership with the Brazilian Ministry of Health (the PIs are in direct contact with head members of SVS through WhatsApp and hold annual meetings in Brasilia) has the potential opens doors to future important collaborative links in the virus outbreak research.
Start Year 2019
 
Description University of Sao Paulo Faculty of Medicine in Ribeirao Preto 
Organisation University of Sao Paulo
Department Ribeirão Preto School of Medicine
Country Brazil 
Sector Academic/University 
PI Contribution CADDE has provided expertise, intellectual input and training in portable genomic sequencing at the University of Sao Paulo Faculty of Medicine in Ribeirao Preto between December 2019 and January 2020. Because of our contribution, we were able to provide a clinical, demographic and genomic description of the largest chikungunya cohort ever described to date (manuscript is now under review in New England Journal of Medicine).
Collaborator Contribution The new partnership with the University of Sao Paulo Faculty of Medicine in Ribeirao Preto (Prof. Luiz Tadeu Moraes Figueiredo, Chair Professor of the Virology Research Centre) has placed CADDE at the epicenter of arbovirus top research in Sao Paulo state and Brazil. Dr. William Souza from Prof. Figueiredo team has led a small group that involved several CADDE team members in a detailed investigation of the largest cohort of chikungunya fatal cases ever reported. This new collaboration with Dr. de Sousa has brought IMT-USP and Oxford together with teams from Northeast Brazil. Together with the new partnerships, we are now generating additional data that will deliverable new insights into the spread of the chikungunya virus in the northeast region (deliverable 9).
Impact The collaboration with the University of Sao Paulo Faculty of Medicine in Ribeirao Preto has resulted in access to additional chikungunya data. Moreover, Dr. William de Souza's impressive application has been selected among 18 international candidates and Dr. William will start his postdoc in Oxford in April 2020.
Start Year 2019
 
Description Brazilian and Oxford scientists sequence the new coronavirus detected in Sao Paulo 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact TV Globo is the largest TV channel in Latin America. TV Globo reported the findings from the CADDE project related to preliminary analyses of the sequence of the first case (http://virological.org/t/first-cases-of-coronavirus-disease-covid-19-in-brazil-south-america-2-genomes-3rd-march-2020/409). With CADDE, it took us 2 days to get from sample to sequence, while this takes an average of 15 days in other countries.
Year(s) Of Engagement Activity 2020
URL https://g1.globo.com/bemestar/coronavirus/noticia/2020/02/28/cientistas-do-brasil-e-de-oxford-sequen...
 
Description Coronavirus emergency declared 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview about the WHO declaration of coronavirus as a public health emergency of international concern.
Year(s) Of Engagement Activity 2020
URL https://www.publico.pt/2020/01/30/ciencia/noticia/coronavirus-oms-declara-emergencia-global-saude-pu...
 
Description First Genomic Epidemiology CADDE Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact We organized the First CADDE Genomic Epidemiology Workshop between the 2 to 6 December 2019) as a hands-on training course based on integrating virus sequencing data generated onsite with state of the art phylogenetic data analysis for outbreak investigation. The event was extremely successful and brought together over 70 people from >15 nationalities. New protocols were tested and at the request of the Brazilian Ministry of Health outbreak team, our collaborators from the ARTIC project presented their lab in a suitcase. This workshop sparked several questions and discussions during the daily poster sessions and afterwards. Several students have stayed in touch requesting new collaborations to be made throughout the Americas (Ecuador, Colombia, Mexico and Panama).
Year(s) Of Engagement Activity 2020
URL https://twitter.com/CaddeProject/status/1203106944313106432?s=20
 
Description Gene sleuths are tracking the coronavirus outbreak as it happens 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Several groups from around the world have seen the MIT Review highlighting our work in Brazil and have contacted us to support rapid sequencing in their countries. Moreover, this has also been noted by representatives of the World Health Organization who informally mentioned the global impact of our achievement due to several media outlets, including this MIT Review.
Year(s) Of Engagement Activity 2020
URL https://www.technologyreview.com/s/615317/gene-sleuths-are-tracking-the-coronavirus-outbreak-as-it-h...
 
Description Guidelines for international COVID19 genome sequencing (World Health Organization) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Pi Nuno Faria has been requested by the World Health Organization to lead the international guidelines for COVID19 genome sequencing.
Year(s) Of Engagement Activity 2020
 
Description How to trace virus histories to stop new outbreaks 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Media interview to discuss to wider public how genetic data can help us to prevent new outbreaks.
Year(s) Of Engagement Activity 2019
URL https://saude.abril.com.br/medicina/entrevista-como-entender-o-passado-dos-virus-para-impedir-novos-...
 
Description Invited seminar at InDRE - Mexican Ministry of Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact About 30 people attended an invited seminar. A strategic meeting with the Director of InDRE was held to formalize collaboration between CADDE and Mexican Ministry of Health.
Year(s) Of Engagement Activity 2020
 
Description Invited seminar at MRC Glasgow, United Kingdom 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Invited talk to discuss new CADDE collaborations with the MRC-University of Glasgow Centre for Virus Research. Four new collaborations have been made during a 6 hour-long visit to MRC-University of Glasgow Centre for Virus Research that will bring advances and will complement some of CADDE's main goals.
Year(s) Of Engagement Activity 2020
 
Description Plenary at the Universidade Federal do Oeste do Pará, Santarém, Brazilian Amazon 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Plenary talk at the Universidade Federal do Oeste do Pará, Santarém, Brazilian Amazon. A full room of nearly 100 students attended the talk which had a visible impact in the community. It stimulated younger generations to ask questions and established new collaborative links that will be important for understanding yellow fever origins in the Amazon and testing metagenomic approaches to discover new viruses.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/CaddeProject/status/1205487167486808064?s=20
 
Description Press release Science Minister Amanda Solloway 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Our CADDE achievements have been quoted by the Science Minister Amanda Solloway who said (press release March 11, 2020):

"UK experts are leading the scientific and medical response to the global coronavirus outbreak, and we were one of the first countries to establish a laboratory test for the virus.

"By decoding the strain discovered in Latin America, the virus is giving up its secrets - giving scientists new insights into its origins, its travels and who has been infected. This will help accelerate the development of medicines, vaccines and strategies to combat it."
Year(s) Of Engagement Activity 2020
 
Description Rapid data sharing and its impact in research 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Opinion article on how rapid sharing of genomes can help reshape public health.
Year(s) Of Engagement Activity 2020
URL https://www.publico.pt/2020/01/24/ciencia/opiniao/partilha-rapida-genomas-virais-surto-impacto-imedi...
 
Description Rapid genome sequencing contributes to vaccine development 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Globo News, an audience leader among TV news channels, interviewed Prof. Ester Sabino, CADDE PI in Brazil, on sequencing and analyzing the first coronavirus cases in South America in less than 48 hours. The interview focused on the impact of virus genomic data for vaccine design and has potentially reached millions of viewers.
Year(s) Of Engagement Activity 2020
URL http://g1.globo.com/globo-news/videos/v/especialista-sobre-coronavirus-genoma-contribui-bastante-pro...
 
Description TV News / Interviews / Podcast / Magazine Articles (28-29 February 2020) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Emai from FAPESP director highlighting FAPESP press release and the outstanding media attention given in Brazil to the CADDE project:

---------- Forwarded message ---------
From: Carlos Henrique de Brito Cruz
Date: Mon, Mar 2, 2020 at 4:38 PM
Subject: RE: parabéns
To: sabinoec@gmail.com
Cc: Walter Colli


Olá Ester
Achei que vc gostaria de ver a lista de repercussões que a Agencia FAPESP coligiu sobre o sequenciamento do vírus.

02 de março de 2020
Notícias pautadas pela Agência FAPESP, revista Pesquisa FAPESP, boletim Pesquisa para Inovação e por ações da Assessoria de Comunicação da Fundação



TECNOLOGIA PERMITIRÁ MONITORAR EPIDEMIA CORONAVÍRUS EM TEMPO REAL

- Notícia sobre metodologia que permitiu pesquisadores do Instituto Adolfo Lutz realizarem o sequenciamento completo do genoma viral, nomeado de SARS-CoV-2, apenas dois dias após o primeiro caso de coronavírus da América Latina ter sido confirmado na capital paulista. A equipe do Adolfo Lutz foi treinada por pesquisadores da USP e da Universidade de Oxford (Reino Unido) que integram uma rede internacional de pesquisa chamada Centro Conjunto Brasil-Reino Unido para Descoberta, Diagnóstico, Genômica e Epidemiologia de Arbovírus (CADDE, na sigla em inglês). Essa rede, que estava articulada para responder e analisar em tempo real epidemias de arboviroses, transferiu para os colegas do Instituto o conhecimento sobre uma tecnologia portátil e barata, conhecida como MinION, que havia sido utilizada no monitoramento da epidemia de Zika nas Américas, por exemplo. O CADDE conta com apoio da FAPESP, Medical Research Council (MRC), UK Research and Innovation (UKRI) e Newton Fund. Além de ajudar a entender como o coronavírus está se dispersando pelo mundo, as informações obtidas com o sequenciamento serão úteis para o desenvolvimento de vacinas e testes diagnósticos

TV Globo - 28 de fevereiro - Jornal Nacional
O Globo - 29 de fevereiro - Sociedade - Pág. 40
O Globo online - 28 de fevereiro
A Tarde (BA) online - 29 de fevereiro
Portal do Governo do Estado de São Paulo - 28 de fevereiro
IstoÉ online - 28 de fevereiro
G1 - 28 de fevereiro
Repercussão a partir da publicação do G1
IG - 28 de fevereiro - Saúde
O Estado de S. Paulo - 01 de março - Metrópole - Pág. A12 (sem citação à FAPESP)
Estadão.com - 29 de fevereiro (sem citação à FAPESP)
O Estado de S. Paulo - 29 de fevereiro - Metrópole - Pág. A19
Estadão.com - 29 de fevereiro
Estadão.com - 28 de fevereiro
Agência Estado - 28 de fevereiro
Repercussão a partir da publicação da Agência Estado
IstoÉ online - 29 de fevereiro
IstoÉ Dinheiro online - 29 de fevereiro
UOL - 29 de fevereiro - Cotidiano
UOL - 29 de fevereiro - VivaBem
BOL - 29 de fevereiro
Terra - 28 de fevereiro
Portal Exame - 28 de fevereiro
Jovem Pan - 28 de fevereiro
Diário do Grande ABC online - 29 de fevereiro
Correio Popular online - 29 de fevereiro
Diário da Região (São José do Rio Preto, SP) online - 28 de fevereiro
SBT Interior - 29 de fevereiro
Diário do Nordeste online - 29 de fevereiro
O Estado de Minas - 29 de fevereiro - Nacional - Pág. 8
Estado de Minas online - 29 de fevereiro
O Povo online - 28 de fevereiro
Correio Braziliense online - 28 de fevereiro
Jornal de Brasília online - 28 de fevereiro
O Dia (Rio de Janeiro, RJ) online - 28 de fevereiro
A Crítica (MS) online - 29 de fevereiro
Diário de Pernambuco online - 29 de fevereiro
Diário de Pernambuco online - 28 de fevereiro
Folha de S.Paulo - 29 de fevereiro - Saúde - Pág. B2
Folha.com - 28 de fevereiro
Repercussão a partir da publicação da Folha de S.Paulo
Yahoo! - 29 de fevereiro
O Tempo - 29 de fevereiro - Especial - Coronavírus - Pág. 9
O Tempo online - 28 de fevereiro
Zero Hora online - 28 de fevereiro
Jornal do Comércio (RS) online - 28 de fevereiro
Folha de Pernambuco online - 28 de fevereiro
A Tribuna (ES) online - 28 de fevereiro
BBC Brasil - 29 de fevereiro
Repercussão a partir da publicação da BBC Brasil
G1 - 29 de fevereiro - Bem Estar
UOL - 29 de fevereiro - Notícias
BOL - 29 de fevereiro
Terra - 29 de fevereiro
Portal R7 - 29 de fevereiro
Yahoo! - 29 de fevereiro
Agência Brasil - 29 de fevereiro (sem citação à FAPESP)
Repercussão a partir da publicação da Agência Brasil
UOL - 29 de fevereiro (sem citação à FAPESP)
BOL - 29 de fevereiro (sem citação à FAPESP)
IstoÉ online - 29 de fevereiro (sem citação à FAPESP)
IstoÉ Dinheiro online - 29 de fevereiro (sem citação à FAPESP)
Dinheiro Rural online - 29 de fevereiro (sem citação à FAPESP)
Diário de Pernambuco online - 29 de fevereiro (sem citação à FAPESP)
Repercussão a partir da publicação da Agência EFE
El Mercurio de Chile On Line (Chile) - 29 de fevereiro
Noticieros Televisa (México) - 29 de fevereiro
Noticiero Pty - 29 de fevereiro
El New York Times (Venezuela) - 29 de fevereiro
LasVerdades.NET (República Dominicana) - 29 de fevereiro
El Dateado - 29 de fevereiro
Noticias Sin (República Dominicana) - 28 de fevereiro
El Siglo (México) - 28 de fevereiro
Milenio (México) - 28 de fevereiro
El Tocuyo al Dia (Venezuela) - 28 de fevereiro


-------------------------------------------------

Carlos Henrique de Brito Cruz

Diretor Científico

FAPESP
Year(s) Of Engagement Activity 2020
 
Description Yellow fever outbreak 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview to a general audience about how ongoing research in yellow fever can help us to prevent and anticipate the forthcoming outbreaks.
Year(s) Of Engagement Activity 2019
URL https://epoca.globo.com/novo-surto-de-febre-amarela-vira-em-cinco-anos-diz-pesquisador-de-oxford-237...
 
Description Yellow fever, dengue, Zika and chikungunya circulation in Brazil 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Media interview to discuss current arbovirus surveillance activities in Sao Paulo.
Year(s) Of Engagement Activity 2019
URL https://www.uol.com.br/vivabem/noticias/redacao/2019/07/29/febre-amarela-dengue-zika-e-chikungunya-q...