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.

Publications

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