This proposal aims to investigate host and microbial genomic determinants of febrile illness in West Africa and establish the West African GEnomic Research (WAGER) Network, consisting of West African Francophone and Anglophone centers of excellence in Nigeria, Sierra-Leone and Senegal. The partners in these three countries have a long-term track record of successful collaboration with each other and with US partners at the Broad Institute, Harvard University, and Tulane University studying the devastating diseases Lassa fever (LF) and Plasmodium falciparum malaria. Moreover, we have a demonstrated deep investment in capacity building and training of African scientists. We recognize that in order to truly participate in this genomic revolution, African researchers must be equipped not only to enable large-scale genomics projects, but also to carry out fully independent research projects, from beginning to end. Febrile illness in Africa is a devastating burden to the continent, and its study is a place in which both large-scale consortium projects and small field studies can have a major impact. In this proposal we will greatly enhance efforts for training and supporting cutting-edge genomics research on health in Africa. We will carry our annual rigorous trainings at the Broad Institute and at WAGER sites and develop them into a larger training program that can be used by all H3Africa partners. We will create a core genomics center at Redeemer's University with an lllumina MiSeq and lay the groundwork to collect 750 high quality samples from febrile patient per year from each of the three WAGER field sites. With these foundations in place, we will use both field-deployed and state-of-the-art genomic technology to identify pathogens driving febrile illness and to examine the genetic basis of infectious disease susceptibility. We will do this through four projects two of which are focused on field-deployable genomic diagnostics and can be carried out at the local sites. The projects are (1) Identifying Microbes Underlying Fever of Unknown Origin (FUO) Through Field Diagnostics;(2) Characterizing FUO through Microbial Metagenomics;(3) Examining Human Genetic Determinants of LF and Malaria;and (4) Identifying Human Genetic Determinants of LF Through Genome-Wide Association.
Febrile illnesses are among the most common causes of morbidity and mortality in Africa. By implementing field deployable genomic tools for microbial infection and host markers, we can begin to understand these diseases and create a foundation for African scientists to pursue research projects in their own countries. Our teams have a long track record of capacity building in Africa around the study of infectious diseases, and have designed our proposal to have the largest impact in terms of research, sustainability, and scalability.
| Siddle, Katherine J; Eromon, Philomena; Barnes, Kayla G et al. (2018) Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018. N Engl J Med 379:1745-1753 |
| Okokhere, Peter O; Erameh, Cyril O; Alikah, Francis et al. (2018) Acute Lassa Virus Encephalitis with Lassa Virus in the Cerebrospinal Fluid but Absent in the Blood: A Case Report with a Positive Outcome. Case Rep Neurol 10:150-158 |
| Dudas, Gytis; Carvalho, Luiz Max; Bedford, Trevor et al. (2017) Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature 544:309-315 |
| Sowunmi, Akintunde; Akano, Kazeem; Ayede, Adejumoke I et al. (2017) Early rising asexual parasitaemia in Nigerian children following a first dose of artemisinin-based combination treatments of falciparum malaria. BMC Infect Dis 17:110 |
| Goba, Augustine; Khan, S Humarr; Fonnie, Mbalu et al. (2016) An Outbreak of Ebola Virus Disease in the Lassa Fever Zone. J Infect Dis 214:S110-S121 |
| Yozwiak, Nathan L; Happi, Christian T; Grant, Donald S et al. (2016) Roots, Not Parachutes: Research Collaborations Combat Outbreaks. Cell 166:5-8 |
| Folarin, Onikepe A; Ehichioya, Deborah; Schaffner, Stephen F et al. (2016) Ebola Virus Epidemiology and Evolution in Nigeria. J Infect Dis 214:S102-S109 |
| Robinson, James E; Hastie, Kathryn M; Cross, Robert W et al. (2016) Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits. Nat Commun 7:11544 |
| Park, Daniel J; Dudas, Gytis; Wohl, Shirlee et al. (2015) Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone. Cell 161:1516-26 |
| Stremlau, Matthew H; Andersen, Kristian G; Folarin, Onikepe A et al. (2015) Discovery of novel rhabdoviruses in the blood of healthy individuals from West Africa. PLoS Negl Trop Dis 9:e0003631 |
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