Phylogeography and reassortment patterns of human influenza A viruses in sub-Saharan Africa

Background. The role of sub-Saharan Africa in the global spread of influenza viruses remains unclear due to insufficient spatiotemporal sequence data. Methods. Here, we analyzed 222 codon-complete sequences of influenza A viruses (IAVs) sampled between 2011 and 2013 from five countries across sub-Saharan Africa (Kenya, Zambia, Mali, Gambia, and South Africa); these genomes were compared with 1,209 contemporaneous global genomes using phylogeographical approaches. Results. The spread of influenza in sub-Saharan Africa was characterized by (i) multiple introductions of IAVs into the region over consecutive influenza seasons, with viral importations originating from multiple global geographical regions, some of which persisted in circulation as intra-subtype reassortants for multiple seasons, (ii) virus transfer between sub-Saharan African countries, and (iii) virus export from sub-Saharan Africa to other geographical regions. Conclusion. Despite sparse data from influenza surveillance in sub-Saharan Africa, our findings support the notion that influenza viruses persist as temporally structured migrating metapopulations in which new virus strains can emerge in any geographical region, including in sub-Saharan Africa; these lineages may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied sub-Saharan Africa regions is required to inform vaccination strategies in those regions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement neumonia Etiology Research for Child Health (PERCH) was supported by the Bill and Melinda Gates Foundation (grant number 48968 to the International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health). This work was also supported through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The study was also part funded by a Wellcome Trust grant [1029745] and a USA CDC grant [GH002133]. The paper is published with the permission of the Director of KEMRI. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Scientific and ethical clearance for the study was obtained from institutional ethics review boards within each study country in Africa, the UK, and USA. Ethical approval was sought and received from KEMRI Scientific Steering Committee (SSC# 1055 and 1433) and Oxford Tropical Research Ethics Committee (OxTREC# Ethics ID:60-90). Informed consent was sought and received from the study participants for the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All generated sequence data were deposited in the Global Initiative on Sharing All Influenza Data (GISAID) EpiFluTM database (https://platform.gisaid.org/epi3/cfrontend) under the accession numbers EPI\_ISL\_509524-EPI\_ISL\_509526, EPI\_ISL\_509564-EPI\_ISL\_509566, EPI\_ISL\_509655- EPI\_ISL\_509669, EPI\_ISL\_509687, EPI\_ISL\_510040-EPI\_ISL\_510043, EPI\_ISL\_510078- EPI\_ISL\_510080, EPI\_ISL\_510102, EPI\_ISL\_510152-EPI\_ISL\_510159, EPI\_ISL\_509025-EPI\_ISL\_509058, EPI\_ISL\_509396-EPI\_ISL\_509411, and EPI\_ISL\_511774-EPI\_ISL\_511804