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ABSTRACT
Dengue is often misclassified and underreported in Africa due to inaccurate differential diagnoses of nonspecific febrile illnesses such as malaria, sparsity of diagnostic testing and poor clinical and genomic surveillance. There are limited reports on the seroprevalence and genetic diversity of dengue virus (DENV) in humans and vectors in Nigeria. In this study, we investigated the epidemiology and genetic diversity of dengue in the rainforest region of Nigeria. We screened 515 febrile patients who tested negative for malaria and typhoid fever in three hospitals in Oyo and Ekiti States in southern Nigeria with a combination of anti-dengue IgG/IgM/NS1 rapid test kits and metagenomic sequencing. We found that approximately 28% of screened patients had previous DENV exposure, with the highest prevalence in persons over sixty. Approximately 8% of the patients showed evidence of recent or current infection, and 2.7% had acute infection. Following sequencing of sixty samples, we assembled twenty DENV-1 genomes (3 complete and 17 partial). We found that all assembled genomes belonged to DENV-1 genotype III. Our phylogenetic analyses showed evidence of prolonged cryptic circulation of divergent DENV lineages in Oyo state. We were unable to resolve the source of DENV in Nigeria owing to limited sequencing data from the region. However, our sequences clustered closely with sequences in Tanzania and sequences reported in Chinese with travel history to Tanzania in 2019. This may reflect the wider unsampled bidirectional transmission of DENV-1 in Africa, which strongly emphasizes the importance of genomic surveillance in monitoring ongoing DENV transmission in Africa.
Acknowledgement
This work received support from ACEGID laboratory and TED’s Audacious Project, including the ELMA Foundation, MacKenzie Scott, and the Skoll Foundation. This work was supported by grants from the National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov), award numbers U01HG007480 to C.T.H and U01AI151812 to E.P), NIH-H3Africa (https://h3africa.org) award number U54HG007480. The World Bank grants projects ACE-019 and ACE-IMPACT. This work was also supported by the Rockefeller Foundation (Grant #2021 HTH), the Africa CDC through the African Society of Laboratory Medicine [ASLM] (Grant #INV018978), and the Science for Africa Foundation. The authors thank Mr. Agbaje for facilitating the Ekiti University Teaching Hospital sample collection.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
BAO designed the study and collected the samples; BAO, KEA, PA, TFO, and IO performed the serological assay and the data analysis; JUO, UEG, and PEE performed the molecular assays and whole genome sequencing; JUO, UEG, and EP conducted the bioinformatics; BAO, JUO, UEG, KEA, PA, TFO, IOI and EP wrote the initial draft manuscript; PA and SH performed statistical analysis; AJA, CTH supervised the work and provided mentorship. BAO funded the serological assay; CTH funded the molecular analyses, genomics sequencing and Bioinformatics aspects of the work. All the authors read and approved the final manuscript before submission.
Data availability
The sequenced raw reads for this study and the generated genomes have been deposited in NCBI under BioProject PRJNA979106 with accession numbers OR259173-OR259175 for the dengue genomes.