海南立克次体病的分子流行病学与病原多样性研究

Located in South Chian and close to the South China Sea, Hainan is a key node of the maritime Silk Road in twenty-first century, has a very important strategic position. Because of the unique geographical and ecological environment, there are various tropical diseases and the infectious diseases spectrum has its unique characteristics. Patients with fever of unknown origin (FUO) are common in Hainan. Previous studies showed that rickettsial diseases like tsutsugamushi disease, spotted fever, typhus and Q fever were epidemic in Hainan. But due to the no systematic research on rickettsial diseases in past times, the background and the pathogen spectrum of rickettsial diseases were unclear. No effective preventive, diagnosis and treatment methods for rickettsial diseases of Hainan currently. This will caused difficulties for control and prevent these diseases, also caused the great threaten for the health of population and for the construction of International Tourism Island and national defense construction. In this project, we plan to do a molecular epidemiological survey on pathogens of rickettsial diseases to the samples from FUO cases, high risk population, major wild animal hosts and arthropods from typical geography and ecological environment in Hainan during the next three years by using PCR/RT-PCR，Luminex high-throughput multi-analyte suspension array, culture and isolation, high-throughput genome sequencing technologies. The results of the project will obtain the systematic pathogen spectrum，time-space distribution characteristics of rickettsial diseases. Also obtain the information on diversity, genotype and genetic evolution characteristics of pathogens. This work is very important for suppling plenty resourses for the basic and applied research, for providing scientific data and technological surpports for control of rickettsial diseases in Hainan. It also has a great significance for guaranteeing the health of the population, promoting the construction of International Tourism Island and national defense .

海南地处华南，毗邻南海，战略地位重要。由于独特的地理及生态环境，海南各种热带病高发，传染病谱具有其独特性，不明原因发热患者常见。已知有恙虫病、斑点热、斑疹伤寒及Q热等立克次体病分布，但由于缺乏系统研究，立克次体病本底及病原谱不清，缺乏有效的诊疗及防治措施，对旅游业、经济及国防建设造成潜在威胁。本项目拟在海南典型生境连续3年采取不明原因发热、高危人群、主要动物宿主及节肢动物媒介样本，应用PCR/RT-PCR、高通量液相芯片技术、分离培养及高通量基因组测序等技术开展立克次体病的分子流行病学调查，结果可获得海南立克次体病本底，掌握立克次体病种类及分布的时空特征，了解立克次体病原的多样性、基因型及其遗传进化特征，发现新病原体，构建立克次体病病原谱及资源库，为立克次体的基础及应用研究提供资源，为立克次体病防治提供科学依据及技术支撑，对保障民众健康、促进经济、旅游及国防建设具有重要意义。

立克次体病(rickettsiosis)是一类主要由虫媒传播、以发热为主要症状、危害严重的人兽共患自然疫源性疾病。海南地处热带，不明原因发热患者常见，由于缺乏系统研究，立克次体病本底及病原谱不清，缺乏有效的诊疗及防治措施，对海南自贸港及国防建设造成潜在威胁。本研究在项目资助下，应用PCR等分子生物学方法对海南不明原因发热、高危人群、主要动物宿主及节肢动物媒介样本开展立克次体病的分子流行病学调查，初步取得以下结果：①完成683份不明原因发热患者恙虫病东方体PCR检测，阳性率为21.08%（144/683）；同源分析表明，海南恙虫病东方体存在Karp、TA763、Kato、Kawaski及Giliam五个基因型，Karp为优势基因型（63.89%，92/144）；②初步构建海南不明原因发热患者及恙虫病东方体资源库；③发现并鉴定海南首例输入性发热伴血小板减少综合症病毒（FSTSV）感染病例；发现并鉴定海南首例狒狒巴莱姆希阿米巴脑炎病例；确诊天疱疹伴粪类圆线虫肺部重度感染病例1例；发现并鉴定海南首例新生儿外耳道蝇蛆病例1例；④在海南人及动物宿主样本中鉴定出毕氏微孢子虫63个ITS基因型，其中38个为新基因型并命名，遗传进化分析大多具有人兽共患特性；在海南部分动物宿主样本中鉴定出13个隐孢子虫虫种和12个基因型，其中6个新亚型及3个新基因型并命名；初步获得海南主要动物宿主及部分人群肠道人兽共患寄生原虫病原谱构成及遗传进化特征，结果提示海南人兽共患肠道原虫的遗传进化具有丰富的多样性及地理隔离特征。⑤发表论文26篇，其中SCI论文11篇、中文综述2篇、国际会议SCI会议论文摘要8篇、e-poster5篇，培养研究生7人青年教师2人。. 项目初步获得海南不明原因发热患者恙虫病东方体感染情况及其基因型，初步构建了海南不明原因发热患者及恙虫病东方体样本库，发现并鉴定海南首例输入性FSTSV病例及狒狒巴莱姆希脑炎等新发病例，初步获得海南主要动物宿主及部分人群肠道人兽共患寄生原虫病原谱构成及遗传进化特征，可为海南相关疾病防治及研究提供科学数据及技术支撑，对保障民众健康、促进海南自贸港及国防建设具有重要意义