2例EV71死亡病例的病理特征及EV71宁波分离株全基因组序列分析

目的探讨2例感染EV71手足口病(HFMD)死亡病例的病理特征及其病原体的分子生物学特征。方法系统分析2例HFMD病例的临床资料及尸检病理结果,并对EV71的PCR结果进行序列分析。结果死者年龄均<3岁,病情进展快,最终出现肺水肿和肺出血死亡。尸检显示:病变主要在中枢神经系统、肺脏以及肠道。大脑及脑干可见明显充血、水肿、炎症、坏死及软化灶等,脑脊膜炎症明显;肺脏显著充血,主要为水肿和出血,肺间质及小血管周围少量炎细胞浸润;肠黏膜充血,空肠及回肠部分区域肠黏膜、黏膜下层、平滑肌层、浆膜均坏死,细胞核消失,胞质及间质溶解,肠壁变薄,肠系膜淋巴结肿大,肠系膜及肠黏膜下淋巴滤泡增生,生发中心坏死;心肌纤维细胞结构正常,心肌间质充血,心肌细胞水肿,心外膜少量炎性细胞浸润;肝、脾、肾、胰腺病理改变不明显。肠内容物及总肠道组织EV 71病毒核酸检测均为阳性。EV 71病毒全基因共7414个碱基,该2株EV71均为C4亚型。结论危重型HFMD(EV 71感染)患者神经系统、呼吸系统病变明显,严重的脑干脑炎、脑膜炎和神经源性肺水肿、肺出血是死亡的主要原因;C4亚型EV71感染的重症HFMD患儿肠道的损害亦极为显著,肠道功能保护不容忽视。

Pathological Features of Two Deaths Caused by Enterovirus 71(EV71) Infection and Whole-genome Sequence Analysis of EV71 Isolated in Ningbo City

Objective To understand pathological features of fatal hand,foot and mouth disease(HFMD) caused by EV71 infection and to analyze whole-genome sequence of EV71 isolated in Ningbo city.Methods The clinical and autopsy data of two deaths caused by EV71 infection were analyzed,and whole-genome sequence of EV71 was analyzed by RT-PCR and sequencing.Results The patients were both younger than 3 years old.Their rapid progression to death was preceded by the development of pulmonary edema and hemorrhage.Results of the autopsy showed that the central nervous system,lung and intestinal were most severely.Changes of the brain and brain stem were congestive,edema,inflammation,necrosis and malacia.The inflammation in meningeal was also significant.There were significant congestion edema and hemorrhage in lung,with small amount of inflammatory cells infiltrated in interstitial lung and around the small blood vessels.There was congestion in intestinal mucosa.Necrosis,nucleus disappears and cytoplasmic solution in mucosa,submucosa,lamina muscularis and serosa were seen in part of the jejunum and ileum.The intestinal wall became meager,with mesenteric lymph nodes enlargement,follicular hyperplasia and germinal center necrosis.Although the structure of myocardial cells were normal,there were congestion in cardiac interstitial,myocardial edema and small amount of inflammatory cells infiltrated in epicardium.No significant pathological changes were seen in other organs such as liver,spleen,kidney and pancreas.Viral nucleic acids of EV71 were detected in intestinal contents and in totalintestinal tissues.The amplified whole-genome sequence of EV71 consists of 7414 base pairs of RNA and the EV71 strains were classified as subgenogroup C4.Conclusion Critical HFMD with EV71 infection often affects central nervous system and lung.Rapid progression to death is preceded by the development of brain stem encephalitis,meningitis,neurogenic pulmonary edema and pulmonary hemorrhage.Severe intestinal damages may relate to EV71 subgenogroup C4 infection and the protection of intestinal function can not be ignored.