本文選題：禽流感　切入點(diǎn)：H7N9　出處：《浙江大學(xué)》2014年博士論文

【摘要】：第一部分甲型H7N9禽流感重癥患者臨床病毒學(xué)研究 背景 2013年2月開始中國(guó)東部地區(qū)開始出現(xiàn)一種新的甲型流感(H7N9)疫情,在3月21日?qǐng)?bào)道第一例確診病例后的短短3個(gè)月時(shí)間內(nèi),一共造成了全國(guó)133例確診感染,其死亡率高達(dá)32%。當(dāng)前對(duì)H7N9禽流感重癥及死亡患者的臨床、血清病毒學(xué)研究還亟待進(jìn)行。 材料及方法 研究納入了2013年4月10日-23日入住本院的確診甲型H7N9禽流感患者中病情嚴(yán)重需要ICU監(jiān)護(hù)的患者。本研究總結(jié)了上述重癥患者的流行病學(xué)特點(diǎn),臨床特征,并對(duì)所有患者的血清、體液、呼吸道分泌物標(biāo)本進(jìn)行病毒學(xué)分析,通過(guò)RT-PCR檢測(cè)病毒核酸,結(jié)果用陽(yáng)性反應(yīng)的循環(huán)數(shù)(Ct值)表示。同時(shí)對(duì)所有患者疾病過(guò)程中的血清進(jìn)行血凝素抑制試驗(yàn),結(jié)果同樣用循環(huán)數(shù)(ct值)表示。最后檢測(cè)了上述患者入院時(shí)和臨床癥狀最嚴(yán)重時(shí)的細(xì)胞因子變化情況。 結(jié)果 研究共納入12名患者,其中6例患者最終死亡,6例患者存活。在死亡患者中,痰標(biāo)本的病毒核酸檢測(cè)結(jié)果水平較鼻咽拭子標(biāo)本更高(ct值中位數(shù)23vs30.5；P=0.08),糞便標(biāo)本中死亡組的6例患者中有4人為陽(yáng)性,比例67%,存活組6例患者中有2例陽(yáng)性,比例為33%。所有患者的血、腦脊液、尿液等其他體液標(biāo)本病毒核酸檢測(cè)均為陰性。所有患者臨床表現(xiàn)均類似,但死亡組患者的繼發(fā)感染比例較存活組高(83%對(duì)50%)。細(xì)胞因子及化學(xué)因子在入院時(shí)及其后的變化情況在死亡組和存活組患者中有顯著差異。 結(jié)論 重癥H7N9禽流感患者中,病毒更趨向于感染下呼吸道,最終臨床結(jié)局為死亡的患者產(chǎn)生HAI抗體產(chǎn)生延遲,且有較高的糞便病毒核酸陽(yáng)性檢出率。 第二部分人感染H7N9禽流感死亡病例的病理學(xué)研究 背景 2013年2月,中國(guó)東部地區(qū)首先爆發(fā)了人感染甲型H7N9禽流感疫情,在其后的1年時(shí)間,共造成了375例患者感染病毒,死亡率超過(guò)2O%。目前尚缺乏系統(tǒng)系分析這一新發(fā)疾病死亡病例的病理學(xué)研究。 材料方法 研究納入了6例2013年3月以來(lái)在本院死亡的H7N9禽流感確診病例。其中4例簽署知情同意書后進(jìn)行死后的細(xì)針穿刺病理學(xué)檢查。光學(xué)顯微鏡下觀察分析肺、心臟、肝臟、脾臟、腎臟、腦、骨髓的病理學(xué)變化,肺組織同時(shí)進(jìn)行免疫組化及電子顯微鏡下的病理學(xué)研究。 結(jié)果 4例患者的肺部表現(xiàn)均提示彌漫性肺泡細(xì)胞損傷�；颊�1于發(fā)病后第8天死亡,肺部病理提示存在肺泡內(nèi)出血表現(xiàn)；患者2及患者3于發(fā)病后第11天后死亡,肺部病理學(xué)表現(xiàn)提示纖維素增生改變；患者4于發(fā)病后45天死亡,肺部病理學(xué)表現(xiàn)提示肺部纖維素沉積,同時(shí)在心臟病理學(xué)觀察中發(fā)現(xiàn)心肌和心內(nèi)膜局灶性淋巴細(xì)胞進(jìn)入性炎癥。上述患者的肺外病理檢查還發(fā)現(xiàn)骨髓的嗜血細(xì)胞現(xiàn)象,脾臟淋巴組織萎縮,這與幾位患者臨床上表現(xiàn)的低淋巴細(xì)胞血癥、低血小板血癥的表現(xiàn)一致。肝臟及腎臟則表現(xiàn)為低氧血癥造成的繼發(fā)性病理改變。 結(jié)論 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綜合癥特征的病理學(xué)表現(xiàn),與人感染H5N1高致病禽流感病毒的病理表現(xiàn)類似。
[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).

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R511.7

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