Identification of virus transmission networks to control key arboviral diseases in Kenya

最近由基孔肯雅病毒、寨卡病毒和登革热病毒引起的史无前例的流行病表明，节肢动物传播的病毒(虫媒病毒)引起的感染是一个重大的全球卫生问题。虽然树枝病毒通常起源于撒哈拉以南非洲，但人们对这些地区的致病病毒谱、流行情况及其社会影响知之甚少。迫切需要更好地了解虫媒病毒传播和维护的生态，以便制定控制措施，限制播种区和世界范围内的关键虫媒病毒病。这一合作项目的主要目标是全面了解肯尼亚的主要虫媒病毒疾病，包括暴发来源、与感染有关的对人类的影响以及虫媒病毒感染的社会条件和后果。研究的所有阶段都把重点放在为非洲学术环境中未来的独立研究提供培训和能力建设上。在第一个资助期内，我们在肯尼亚巴林戈县的沙蝇中检测到四种以前未知的静脉病毒。基于全基因组序列的系统发育分析表明，其中一种病毒名为Ntepe病毒，与Karimabad血清复合体病毒有关，而其他三种病毒与与人类发热性疾病有关的白粉病西西里血清复合体建立了一个新的高度分化的分支。我们可以证明感染Ntepe病毒的新生小鼠会导致致命的疾病，我们在人血清样本中检测到了针对这种病毒的中和抗体。到目前为止，肯尼亚还没有检测到沙蝇传播的静脉病毒。虽然第一个资助期让我们更广泛地了解了几种虫媒病毒在媒介、家鼠、家畜和人中的丰度模式，但第二个资助期将专注于第一个资助期确定的关键虫媒病毒的扩增和传播动态。此外，在第一个资助期内，我们深入了解了虫媒病毒疾病的知晓率、发病率和经济影响。我们现在将利用这些知识来测试合适的干预策略，以开发可持续的基于社区的媒介生物控制策略。主要目标是：(I)研究关键虫媒病毒在媒介和宿主中的传播动力学；(Ii)评估虫媒病毒感染对人类健康和当地社会的影响；(Iii)评估教育和卫生信息对行为改变的影响，以便在不同的社会经济环境中接受目标明确的可持续媒介控制干预策略；(Iv)在疾病生态学、病毒学和社会科学领域提供教育、培训和能力建设。

The recent unprecedent epidemics caused by chikungunya virus, Zika virus and dengue virus have exemplified that infections caused by arthropod-borne viruses (arboviruses) are a major global health problem. While arboviroses often originate in Sub-Saharan Africa, there is little knowledge on the spectrum of causative viruses, their prevalence, and their social impact in these regions. There is an urgent need to better understand the ecology of arbovirus transmission and maintenance, in order to develop control measures that limit key arboviral diseases in the seeding regions and worldwide. The major goal of this collaborative project is a holistic understanding of key arboviral diseases in Kenya, including sources of outbreaks, infection-related impacts on humans, as well as societal conditions and consequences of arbovirus incidence. A strong focus in all stages of research is on training and capacity building for future independent research in an African academic environment.During the first funding period we detected four previously unknown phleboviruses in sandflies in Baringo County, Kenya. Phylogenetic analyses based on complete genome sequences showed that one virus, named Ntepes virus, is related to viruses of the Karimabad serocomplex, whereas the other three viruses established a novel highly diverged clade in sister relationship to the sandfly fever Sicilian serocomplex, which is associated with febrile illness in humans. We could show that infection of new-born mice with Ntepes virus caused fatal illness and we detected neutralizing antibodies against this virus in human serum samples. Sandfly-borne phleboviruses have so far not been detected in Kenya. While the 1st funding period gave us a broader understanding of abundance patterns of several arboviruses in vectors, peri-domestic rodents, livestock and humans, the 2nd funding period will focus on amplification and transmission dynamics of key arboviruses identified in the 1st period. Furthermore, we gained insight into the awareness, incidence and economic impact of arboviral diseases during the 1st funding period. We will now use this knowledge to test suited intervention strategies to develop sustainable community-based vector control strategies. The key objectives are:(i) to study transmission dynamics in vectors and hosts for selected key arboviruses,(ii) to assess the impact of arboviral infections on human health and local society,(iii) to assess the effect of education and health information on behavioural change towards acceptance of well-targeted sustainable vector control intervention strategies in different socio-economic settings,(iv) to provide education, training, and capacity building in the fields of disease ecology, virology, and social sciences.Overall, the project aims to reduce arbovirus disease outbreaks locally and also globally by preventing geographic spread from seeding regions.