甲型H7N9禽流感重症患者临床、病毒学、组织病理学研究

发布时间：2018-03-25 16:20

本文选题：禽流感　切入点：H7N9　出处：《浙江大学》2014年博士论文

【摘要】：第一部分甲型H7N9禽流感重症患者临床病毒学研究背景 2013年2月开始中国东部地区开始出现一种新的甲型流感(H7N9)疫情,在3月21日报道第一例确诊病例后的短短3个月时间内,一共造成了全国133例确诊感染,其死亡率高达32%。当前对H7N9禽流感重症及死亡患者的临床、血清病毒学研究还亟待进行。材料及方法研究纳入了2013年4月10日-23日入住本院的确诊甲型H7N9禽流感患者中病情严重需要ICU监护的患者。本研究总结了上述重症患者的流行病学特点,临床特征,并对所有患者的血清、体液、呼吸道分泌物标本进行病毒学分析,通过RT-PCR检测病毒核酸,结果用阳性反应的循环数(Ct值)表示。同时对所有患者疾病过程中的血清进行血凝素抑制试验,结果同样用循环数(ct值)表示。最后检测了上述患者入院时和临床症状最严重时的细胞因子变化情况。结果研究共纳入12名患者,其中6例患者最终死亡,6例患者存活。在死亡患者中,痰标本的病毒核酸检测结果水平较鼻咽拭子标本更高(ct值中位数23vs30.5；P=0.08),粪便标本中死亡组的6例患者中有4人为阳性,比例67%,存活组6例患者中有2例阳性,比例为33%。所有患者的血、脑脊液、尿液等其他体液标本病毒核酸检测均为阴性。所有患者临床表现均类似,但死亡组患者的继发感染比例较存活组高(83%对50%)。细胞因子及化学因子在入院时及其后的变化情况在死亡组和存活组患者中有显著差异。结论重症H7N9禽流感患者中,病毒更趋向于感染下呼吸道,最终临床结局为死亡的患者产生HAI抗体产生延迟,且有较高的粪便病毒核酸阳性检出率。第二部分人感染H7N9禽流感死亡病例的病理学研究背景 2013年2月,中国东部地区首先爆发了人感染甲型H7N9禽流感疫情,在其后的1年时间,共造成了375例患者感染病毒,死亡率超过2O%。目前尚缺乏系统系分析这一新发疾病死亡病例的病理学研究。材料方法研究纳入了6例2013年3月以来在本院死亡的H7N9禽流感确诊病例。其中4例签署知情同意书后进行死后的细针穿刺病理学检查。光学显微镜下观察分析肺、心脏、肝脏、脾脏、肾脏、脑、骨髓的病理学变化,肺组织同时进行免疫组化及电子显微镜下的病理学研究。结果 4例患者的肺部表现均提示弥漫性肺泡细胞损伤。患者1于发病后第8天死亡,肺部病理提示存在肺泡内出血表现；患者2及患者3于发病后第11天后死亡,肺部病理学表现提示纤维素增生改变；患者4于发病后45天死亡,肺部病理学表现提示肺部纤维素沉积,同时在心脏病理学观察中发现心肌和心内膜局灶性淋巴细胞进入性炎症。上述患者的肺外病理检查还发现骨髓的嗜血细胞现象,脾脏淋巴组织萎缩,这与几位患者临床上表现的低淋巴细胞血症、低血小板血症的表现一致。肝脏及肾脏则表现为低氧血症造成的继发性病理改变。结论人感染甲型H7N9禽流感病毒死亡患者符合肺源性的急性呼吸窘迫综合症特征的病理学表现,与人感染H5N1高致病禽流感病毒的病理表现类似。
[Abstract]:The first part of the clinical virology study of severe patients with H7N9 avian influenza
background
February 2013 began in the eastern region of Chinese the emergence of a novel influenza A (H7N9) outbreak in March 21st reported the first confirmed cases after just 3 months, a total of 133 cases caused the infection, the mortality rate is as high as 32%. on the current clinical death and severe H7N9 flu patients, serum virology research needs to be done.
Materials and methods
The study included patients admitted to our hospital on April 10, 2013 -23 confirmed cases of H7N9 avian influenza in patients with severe ICU patients need to care. This study summarizes the epidemiological characteristics, clinical features of these patients, and the serum of all patients with respiratory tract samples of body fluids, virological analysis by RT-PCR viral nucleic acid detection, with positive results the reaction cycle number (Ct value) said. At the same time, all patients serum disease in the process of hemagglutinin inhibition test results with the same number of cycles (CT) said. Finally detect the cytokine changes of the patients on admission and clinical symptoms was most severe.
Result
The study included 12 patients, including 6 patients died, 6 patients survived. On the death of patients, viral nucleic acid detection results of sputum levels than nasopharyngeal swabs were higher (median CT value 23vs30.5; P=0.08), fecal samples 6 cases death group in 4 of the patients were positive. The proportion of 67%, the survival group in 6 cases, 2 cases were positive for 33%., the proportion of all patients with blood, cerebrospinal fluid, urine and other fluid samples of virus nucleic acid detection were negative. The clinical manifestations of all patients were similar, but the death of patients with secondary infection rate higher than the survival group (83% to 50%). Cytokines and chemical factors at admission and after changes in the death group and survival group. There was significant difference
conclusion
In patients with severe H7N9 avian influenza, the virus tends to infect the lower respiratory tract. The final clinical outcome is delayed HAI antibody production and high fecal virus nucleic acid positive rate.
Pathological study on second deaths of human H7N9 avian influenza
background
In February 2013, a case of human infection with avian influenza A (H7N9) broke out in the eastern part of China. In the next 1 years, 375 patients were infected with the virus and the mortality rate was over 2O%..
Material method
The study included 6 patients since March 2013 in our hospital confirmed cases of H7N9 avian flu deaths. Among the 4 cases of informed consent after fine needle aspiration pathology of postmortem examination. Lung analysis, optical microscopy of heart, liver, spleen, kidney, brain, bone marrow pathological changes of lung tissue and pathological. Immunohistochemical and electron microscopic studies.
Result
4 cases of patients with pulmonary manifestations showed diffuse alveolar cell injury. 1 patients in eighth days after the onset of death, lung pathology suggests the presence of intra alveolar hemorrhage in 2 patients and 3 patients; in eleventh days after the onset of death, lung pathological findings in 4 patients with hyperplasia of cellulose; 45 days after the onset of death, lung pathology findings indicate that lung cellulose deposition, while observation of cardiac pathology found in lymphocytes of myocardium and endocardium in focal inflammatory pulmonary pathological examination. These patients also found hemophagocytic phenomenon of bone marrow, spleen and lymph tissue atrophy, and the low blood lymphocyte performance several patients clinically, low platelet count the performance is consistent. Liver and kidney showed hypoxemia caused by secondary pathological changes.
conclusion
The death of patients infected with avian influenza A (H7N9) accords with the pathological characteristics of acute respiratory distress syndrome characterized by pulmonary origin, which is similar to the pathological findings of human highly pathogenic avian influenza virus (H5N1).

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R511.7

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