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前所未有的流行病已经证明，由节肢动物传播的病毒（虫媒病毒）引起的感染是一个主要的全球健康问题。虽然虫媒病毒通常起源于撒哈拉以南非洲，但对这些地区的致病病毒谱、流行率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持的生态学，以便制定控制措施，限制播种地区和世界范围内的关键虫媒病毒疾病。该合作项目的主要目标是全面了解肯尼亚的关键虫媒病毒疾病，包括疫情来源、与感染相关的对人类的影响以及虫媒病毒发病的社会条件和后果。在研究的所有阶段的一个强烈的重点是在非洲学术环境的未来独立研究的培训和能力建设。在第一个资助期间，我们发现了四个以前未知的白蛉病毒在巴林戈县，肯尼亚。基于全基因组序列的系统发育分析表明，一种名为Ntepes病毒的病毒与Karimabad血清复合体的病毒有关，而其他三种病毒则与与人类发热性疾病相关的白蛉热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，新生小鼠感染Ntepes病毒会导致致命的疾病，我们在人类血清样本中检测到针对该病毒的中和抗体。到目前为止，在肯尼亚尚未发现白蛉传播的白蛉病毒。虽然第一个资助期使我们更广泛地了解了病媒、围家啮齿动物、牲畜和人类中几种虫媒病毒的丰度模式，但第二个资助期将侧重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，我们在第一个资助期内深入了解了虫媒病毒疾病的意识，发病率和经济影响。我们现在将利用这些知识来测试适当的干预战略，以制定可持续的社区病媒控制战略。主要目标是： 研究选定的关键虫媒病毒在病媒和宿主中的传播动态，（ii） 评估虫媒病毒感染对人类健康和当地社会的影响，（iii） 评估教育和健康信息对不同社会经济环境中行为变化的影响，以使人们接受目标明确的可持续病媒控制干预战略，㈣ 提供疾病生态学、病毒学和社会科学领域的教育、培训和能力建设。总的来说，该项目旨在通过防止虫媒病毒从播种地区的地理传播，减少地方和全球的虫媒病毒疾病爆发。

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.