微小巴贝西虫和嗜吞噬细胞无形体复合感染的致病特征研究

Babesia microti and Anaplasma phagocytophilum are two tick-borne pathogens and have been recognized as emerging human pathogens of public health relevance. The coinfection with B. microti and A. phagocytophilum has been observed in animal reservoirs, tick vectors and humans in recent studies. Epidemiologic investigations on infection prevalence of the two pathogens have been performed in animal reservoirs and tick vectors in China, but their pathogenetic and immunologic characteristics remain unclear and no study focuses on the coinfection with B. microti and A. phagocytophilum. We have detected the coinfection with B. microti and A. phagocytophilum in a small rodent and maintained the pathogens through propagation in experimental mice in previous study. The present program was designed to construct the singly infected and coinfected mouse model. Clinical signs, pathogen loads, spleen weights, hematologic and clinical chemistry parameters, and histopathological changes were monitored experimentally for a long term to compare disease severity in singly infected and coinfected mice. Antibody and cytokine levels were measured to determine whether disease severity correlated with immune response. These results will reveal pathogen infection progress, host immune response and pathogenetic characteristics of the coinfection with B. microti and A. phagocytophilum. This program will help lay a foundation for prevention and control of diseases and related clinical diagnosis, provide scientific basis for researching coinfection with Babesia and Anaplasma, and promote in-depth understanding of coinfection among tick-borne pathogens.

微小巴贝西虫和嗜吞噬细胞无形体是两种新发蜱传病原体，近年国外研究发现宿主动物、媒介蜱及人群中均存在这两种病原体的复合感染。国内关于这两种新发蜱传病原体的研究多为宿主动物及媒介生物的感染调查，对我国自然疫源地来源并流行的病原体尚未开展深入研究，其复合感染研究更是缺乏。本课题前期研究已从我国河南信阳的啮齿类动物中发现微小巴贝西虫和嗜吞噬细胞无形体的复合感染，并分离到病原体。在此基础之上，本研究进一步建立单独感染与复合感染的小鼠模型，并连续监测感染小鼠的体征、病原体感染载量、抗体及细胞因子水平、血象、血生化以及组织病理变化等指标，比较分析复合感染与单独感染的差异，旨在阐明微小巴贝西虫和嗜吞噬细胞无形体复合感染的病原变化规律、宿主免疫反应及致病特征。本研究可为我国相关蜱媒传染病的预防控制及临床诊疗奠定科学基础，为巴贝西虫和无形体的复合感染研究提供重要科学参考，促进对蜱媒传染病复合感染的深入认识。

微小巴贝西虫和嗜吞噬细胞无形体是两种新发蜱传病原体，近年国外研究发现宿主动物、媒介蜱及暴露人群中均存在这两种病原体的复合感染。国内关于这两种新发蜱传病原体的研究甚少，主要为宿主动物及媒介生物的感染调查，对我国自然疫源地来源并流行的病原体尚未开展深入研究，其复合感染研究更是缺乏。本课题前期研究已从我国河南信阳的啮齿类动物中发现微小巴贝西虫和嗜吞噬细胞无形体的复合感染，并分离到病原体。在此基础之上，本项目建立了单独感染与复合感染的小鼠模型，揭示了两种病原体单独感染与复合感染的病原体变化规律、免疫反应以及感染致病特征。结果发现在复合感染微小巴贝西虫的情况下，嗜吞噬细胞无形体感染载量可长时间维持在高位，提示若发生嗜吞噬细胞无形体感染和微小巴贝西虫的复合感染，那么患者感染嗜吞噬细胞无形体的病程将会延长，并且可能会加重疾病病情；在先感染嗜吞噬细胞无形体的情况下，微小巴贝西虫的感染高峰会提前，且感染载量可增高两倍以上，提示若感染嗜吞噬细胞无形体患者在未经治疗情况下，短时间内再次感染微小巴贝西虫，那么患者可能会表现出严重的寄生虫血症，并可能引起严重的临床表现。两种病原体的复合感染也能导致实验小鼠出现更为严重的炎症反应、血小板减少、红细胞减少、血红蛋白降低及脾肿大等情况，反应了复合感染会加重疾病进展。本项目的研究发现为我国巴贝西虫和无形体的复合感染的预防控制及临床诊疗提供重要科学参考，促进了对蜱媒传染病复合感染的深入认识。项目研究结果警示临床上应当加强微小巴贝西虫和嗜吞噬细胞无形体复合感染的监测，重视并注意鉴别复合感染，若发现临床病例存在复合感染，需注意嗜吞噬细胞无形体感染的病程将会延长，应当考虑适当延长多西环素治疗时间，也需注意微小巴贝西虫感染的寄生虫血症会提前且更为严重，应当考虑尽早开展抗虫治疗。