人类肠腺病毒种类F(HAdV-F)是儿童腹泻死亡的主要原因。基因组分析将是理解传播动力学的关键,疾病严重程度的潜在驱动因素,和疫苗开发。然而,目前,全球HAdV-F基因组数据有限。这里,我们对2013年至2022年在肯尼亚沿海收集的粪便样本中的HAdV-F进行了测序和分析。样本是在肯尼亚沿海的Kilifi县医院从13岁以下的儿童中收集的,这些儿童在过去24小时内报告了三个或更多的粪便。通过系统发育分析和突变谱分析分析了基因组以及来自世界其他地区的数据。基于与先前描述的标准和命名法一致的系统发育聚类来分配类型和谱系。参与者的临床和人口统计学数据与基因型数据相关联。在使用实时聚合酶链反应确定的91例病例中,组装了88个接近完整的基因组,分别分为HAdV-F40(n=41)和HAdV-F41(n=47)。这些类型在整个研究期间共同传播。HAdV-F40(谱系1-3)和HAdV-F41(谱系1,2A,3A,3C,和3D)。在五个样品中观察到F40和F41型共感染,在一个样品中观察到F41和B7型共感染。两名F40和41合并感染的儿童也感染了轮状病毒,并患有使用Vesikari评分系统定义的中度和重度疾病,分别。在谱系1和3之间出现的四个HAdV-F40序列中发现了异型重组。HAdV-F41病例均无黄疸。这项研究提供了广泛的遗传多样性的证据,合并感染,在肯尼亚沿海农村的HAdV-F40中进行重组,这将为公共卫生政策提供信息,疫苗开发,包括局部循环谱系,和分子诊断试验的发展。我们建议未来进行全面研究,阐明HAdV-F遗传多样性和免疫力,以开发合理的疫苗。
Human enteric adenovirus species F (HAdV-F) is a leading cause of childhood diarrhoeal deaths. The genomic analysis would be key to understanding transmission dynamics, potential drivers of disease severity, and vaccine development. However, currently, there are limited HAdV-F genomic data globally. Here, 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 coastal Kenya from children <13 years of age who reported a history of three or more loose stools in the previous 24 hours. The genomes were analysed together with the data from the rest of the world by phylogenetic analysis and mutational profiling. Types and lineages were assigned based on phylogenetic clustering consistent with the previously described criteria and nomenclature. Participant clinical and demographic data were linked to genotypic data. Of ninety-one cases identified using real-time Polymerase Chain Reaction, eighty-eight near-complete genomes were assembled, and these were classified into HAdV-F40 (n = 41) and HAdV-F41 (n = 47). These types co-circulated throughout the
study period. Three and four distinct lineages were observed for HAdV-F40 (Lineages 1-3) and HAdV-F41 (Lineages 1, 2A, 3A, 3C, and 3D). Types 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 diseases as defined using the Vesikari Scoring System, respectively. Intratypic
recombination was found in four HAdV-F40 sequences occurring between Lineages 1 and 3. None of the HAdV-F41 cases had jaundice. This
study provides evidence of extensive genetic diversity, coinfections, and
recombination within HAdV-F40 in a rural coastal Kenya 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.