Genomic Characterization and Surveillance of Microbial Threats in West Africa

Principal Investigator:

Overall Recent viral outbreaks in West Africa, specifically the 2013-16 Ebola Virus Outbreak, shed light on the many limitations of current surveillance and diagnostics in the region’s public health systems. Tools for rapid, accurate diagnostics and genomic analysis of patient samples were often not readily available in the areas that were most severely affected by the disease, making it more difficult to reduce morbidity and mortality during the epidemic. There is a need for Africans to get more engaged in locally using the wide array of genomic techniques and data in order to improve patient treatment. . This proposal aims to characterize and survey microbial threats across West Africa, such as Ebola, Lassa fever, and malaria, by building on a long-term collaborative effort among established academic, research and clinical centers in Nigeria (RUN, ISTH), Senegal (UCAD), and Sierra Leone (KGH), along with additional partners in the US at the Broad Institute and Tulane University. The proposed collaborative center will (1) utilize next generation sequencing and microbial metagenomics technologies to identify and characterize the nature and extent of circulating viral pathogens at the study sites; (2) develop robust and cost-effective field diagnostics, using both molecular and immunoassays to swiftly and accurately capture the prevalence of these pathogens in the population, and (3) use this genomic and immunological data, along with studies on the clinical manifestations of these diseases, to characterize the pathogen-host interaction and enhance clinical care. In addition the proposed project will substantially increase the building capacity for African scientists in the field of genomics, both by improving the technical resources at the project sites and through intensive training in genomics and bioinformatics at both the African and US sites. Specifically, using Illumina MiSeq instruments currently on site in Nigeria and Senegal (and coming soon to Sierra Leone), we will further expand capacity for next generation sequencing and computational analysis.. These activities serve our overall strategic goals of moving more research operations to African sites and empowering African scientists to perform cutting-edge genomic infectious disease research and discovery fully within the continent.

Updated Aims:
AIM 1. Utilize Microbial Metagenomics for Viral Pathogen Characterization:
– Perform pathogen-independent sequencing to identify known, novel, and divergent microbes.
– Characterize the population genetics and basic virology of known, novel, and emerging viruses.
– Enhance methods for more efficient and cost-effective viral sequencing.

AIM 2. Field Diagnostics for Pathogen Surveillance:
– Develop quantitative PCR tests for known and novel pathogens to enhance clinical care.
– Develop immunoassays to allow for rapid diagnosis across many sites.
– Perform surveillance and investigate epidemiology of known and novel pathogens.

AIM 3. Use Clinical, Genomic, and Immunological Data for Studying Viral and Host Biology:
– Examine the clinical manifestations of viral disease and develop tools to enhance clinical care.
– Investigate host genetic determinants of Lassa fever and Ebola virus disease.