Genomic epidemiology of Human Adenovirus F40 and F41 in Coastal Kenya: A retrospective hospital-based surveillance study (2013-2022)

Abstract

AbstractIntroductionHuman adenoviruses type F (HAdV-F) are leading cause of childhood diarrhoeal deaths. Genomic analysis would be key for understanding their potential drivers of disease severity, transmission dynamics, and for vaccine development. However, currently there is only limited data on HAdV-F genomes globally.MethodsHere, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in Kilifi, Kenya, from children < 13 years of age who reported a history of ≥ 3 loose stools in the previous 24hrs. The genomes were compared with data from the rest of the world by phylogenetic analysis and mutational profiling. Genotypes and lineages were assigned based on clustering on the global phylogenetic tree and from previously described nomenclature. Participant clinical and demographic data were linked to genotypic data.ResultsOf 91 cases identified using real-time PCR, 83 near-complete genomes were assembled, and these classified into HAdV-F40 and F41. These genotypes cocirculated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineage 1-3) and F41 (Lineage 1, 2A, 3A, 3C and 3D). Genotype F40 and F41 coinfections were observed in five samples, and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe disease, respectively. Intratypic recombination was found in 4 HAdV-F40 sequences occurring between lineages 1 and 3. None of the HAdV-F41 cases had jaundice.InterpretationThis study provides evidence of extensive genetic diversity, coinfections and recombination within HAdV-F40 in a high adenovirus transmission setting that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.