重症登革热的预警指征及其发病影响因素研究

发布时间：2018-05-11 12:18

本文选题：重症登革热 + 回顾性分析　；参考：《广州医科大学》2013年硕士论文

【摘要】：登革热是一种急性发热性传染病，主要通过蚊媒传播，它的病原体是登革病毒，该病毒有四种血清型（DENV1～4）。登革热的临床表现多种多样，既可表现为普通发热，也可发生致死性的重症。登革出血热和登革休克综合症等重症病例造成每年约20,000例患者死亡，成为影响发展中国家公共健康的一种重要疾病。在我国，登革热主要在沿海地区流行，其中以广东省最为严重，广东几乎每年都有登革热的报道。重症登革热病例病死率高，所以早期发现并对症治疗是救治重症登革热、降低病死率的关键。为了提高重症登革热的诊断成功率，世界卫生组织（World Health Organization，WHO）于2009年发布了新的登革热诊治指南，将登革热的临床分型修改为登革热和重症登革热两大类型，其中登革热又分为无预警征型和有预警征型，并将以下七个表现作为重症预警征(Warningsigns,WS)，包括腹部疼痛或压痛，持续性呕吐，临床血浆渗漏征，皮肤粘膜出血，极度乏力或烦躁，肝脏增大超过2厘米，伴随红细胞压积升高的血小板迅速下降等。该分型方案已在全球多个流行地区的登革热临床诊断中得到了初步应用，大多数研究认为它能较好地指导临床诊治工作，但对其适用性仍存在争议。在我国，这一新的分型方案尚未应用于临床，也未见相关的研究报道。因此，在我国人群中，探讨重症登革热的临床及实验室预警指标，对于制定适用于我国患者的登革热诊治方案、提高登革热的诊治水平具有重要意义，同时也将为WHO发表的新版登革热诊治指南提供有益的补充。迄今为止，登革病毒感染引发重症的原因尚不清楚，大量研究推测其与患者的年龄、性别和基础疾病等宿主因素有关。此外，异型登革病毒的二次感染也可能是导致重症登革热的重要原因。从临床资料、血清学和病毒学三个方面系统分析重症登革热患者病例,将为探寻重症登革热的发病机制和影响因素提供可靠的依据。研究目的 1、总结我国登革热的临床及实验室特征，探讨重症登革热预警指标及2009年版的WHO登革热诊断标准在我国的适用性; 2、分析我国首例重症登革热病例的临床及病原学特征，初步揭示重症登革热的发病机制和影响因素。研究方法 1、回顾性分析1990～2012年广州市第八人民医院收治的登革热患者的临床及实验室资料,得到的数据用临床信息数据分析管理系统进行处理，并统计分析； 2、回顾性分析一例重症登革热病例的临床及实验室检查的特征； 3、采用酶联免疫法（ELISA）检测该病例发病期和恢复期血清登革IgM和IgG抗体，并用蚀斑减少中和试验检测其发病期及恢复期血清中针对不同血清型登革病毒的中和抗体水平。依据抗原原罪现象，确定该病人初次感染的登革病毒血清型； 4、采用WHO推荐的nested RT-PCR法扩增该病例急性期血清中登革病毒的C-prM基因片段，确定其血清型。通过将C-prM基因序列在GenBank中进行Blast比对，确定与该基因同源性最高的登革病毒序列，根据该序列，采用PCR DESIGN软件设计扩增E基因片段的引物，采用RT-PCR法扩增该病例急性期血清中登革病毒的E基因片段，根据E基因序列，利用Neighbor-Joining法对该病毒株和其他29株DENV-1进行系统进化分析，确定该病毒的来源。结果 1、1990年～2012年广州市第八人民医院共收治了1896例登革热患者，其中年龄超过18岁者1647人，占88.3%。诊断为普通登革热者1890例，诊断为登革出血热者5例，诊断为登革休克综合征者1例；按WHO2009诊断标准，诊断登革热者1262例，，诊断为伴预警征的登革热者496例，诊断为重症登革热者138人。138例重症登革热中，出现休克者18例（13.0%），出现体液渗出并呼吸抑制者6例（4.3%），出现严重出血者77例（55.8%），出现谷丙转氨酶或谷草转氨酶升高超过1000U/L者5例（3.6%），出现意识障碍者4例（2.9%），出现心肌炎者31例（22.5%），出现肾功能不全者11例（8.0%）。 2.全部病例中有634例次出现过重症预警征，最常出现的重症预警征为：重度乏力(28.5%)、液体渗出征(15.7%)和皮肤粘膜出血(27.1%)，特异性大于90%的WS包括腹痛(97.3%)、肝脏增大(99.8%)、伴随红细胞压积升高的血小板减少(99.5%)； 3、我们此次报道的国内首例确诊重症登革热的病例是一位68岁的女性，她有糖尿病及高血压病史多年，此次发病后，出现发热、乏力、头痛、全身关节痛，并出现皮肤注射部位瘀斑和消化道出血表现。检查发现她的白细胞和血小板计数明显下降，肝肾功能损害明显，白蛋白降低，B超检查发现胆囊壁增厚。 4、病毒学检测结果显示该重症病人此次感染的登革病毒为DENV-1,属于基因I型，与东南亚流行区的DENV-1同源性最高。 5、血清学检测结果表明该重症病人为登革病毒二次感染，其初次感染的登革病毒为DENV-2。结论 1.在本组1896例病人中，符合重症登革热诊断者138例，与临床表现的严重程度较相符，证明2009年WHO登革热诊断指南较适合我国临床应用。腹痛、肝肿大、体液外渗征、红细胞压积升高伴血小板计数减少等是重症登革热的特异性预警征。 2.老年、女性、合并糖尿病和高血压、以及登革病毒二次感染是本例登革热发生重症的主要因素。腹部彩色B超检查胆囊壁厚度可能可以作为早期诊断重症登革热的指标。
[Abstract]:Dengue fever is an acute febrile infectious disease, mainly transmitted through mosquito vector, its pathogen is dengue virus, the virus has four serotypes (DENV1 to 4). Dengue fever has a variety of clinical manifestations, both common fever and fatal severe cases. Dengue hemorrhagic fever and dengue shock syndrome are caused by severe cases. In China, dengue fever is an important disease affecting public health in developing countries. In China, dengue fever is mainly prevalent in coastal areas. In Guangdong, Guangdong is the most serious, and dengue fever has been reported almost every year in Guangdong. The mortality of severe dengue fever is high, so early discovery and symptomatic treatment are the treatment of severe dengue. In order to improve the diagnostic success rate of severe dengue fever, the WHO (World Health Organization, WHO) issued a new dengue diagnosis and treatment guide in 2009. The clinical classification of dengue fever is modified to two types of dengue fever and severe dengue fever, and dengue fever is divided into no early warning type and early warning. The following seven manifestations were performed as Warningsigns (WS), including abdominal pain or pressure pain, persistent vomiting, clinical plasma leakage, skin and mucous membrane bleeding, extreme fatigue or irritability, liver enlargement more than 2 centimeters, and rapid reduction of platelets with elevated hematocrit, and so on. The clinical diagnosis of dengue fever in the region has been preliminarily applied. Most studies suggest that it can better guide the clinical diagnosis and treatment work, but there are still disputes about its applicability. In our country, this new classification scheme has not been applied to clinical and no related research reports. Therefore, the clinical and actual situation of severe dengue fever is discussed in the population of our country. It is of great significance to make the diagnosis and treatment of dengue fever and to provide useful supplement to the new dengue fever diagnosis and treatment guidelines published by WHO. So far, the cause of dengue virus infection is not clear. A large number of studies have speculated that it and the patient. In addition, the two infection of dengue virus may also be an important cause of severe dengue fever. From three aspects of clinical data, serology and virology, a systematic analysis of the cases of severe dengue fever will be provided to explore the pathogenesis and influencing factors of dengue fever. The basis for it.
research objective
1, summarize the clinical and laboratory characteristics of dengue fever in China, and explore the applicability of the dengue fever early warning indicators in 2009 and the diagnostic criteria of WHO dengue fever in China.
2, analyze the clinical and etiological characteristics of the first severe dengue fever in China, and reveal the pathogenesis and influencing factors of severe dengue fever.
research method
1, the clinical and laboratory data of dengue fever patients in Eighth People's Hospital of Guangzhou in 1990~2012 years were analyzed retrospectively. The data obtained were processed by the clinical information data analysis management system, and the statistical analysis was made.
2, we retrospectively analyzed the clinical and laboratory characteristics of a case of severe dengue fever.
3, the serum dengue IgM and IgG antibodies were detected by enzyme linked immunosorbent assay (ELISA), and the neutralization antibody level for different serotypes of dengue virus was detected by the plaque reduction neutralization test in the onset period and the recovery period.
4, the nested RT-PCR method recommended by WHO was used to amplify the C-prM gene fragment of dengue virus in the acute phase of the case and determine its serotype. By Blast alignment of the C-prM gene sequence in GenBank, the sequence of dengue virus with the highest homology of the gene was determined, and the PCR DESIGN software was used to amplify the E gene fragment according to the sequence. Primers, RT-PCR method was used to amplify the E gene fragment of dengue virus in the acute phase of the case of the case. According to the E gene sequence, the virus strain and 29 other DENV-1 strains were phylogenetic analysis by Neighbor-Joining method, and the source of the virus was determined.
Result
From 11990 to 2012, 1896 cases of dengue fever were treated in Eighth People's Hospital in Guangzhou, of which 1647 people aged 18 years old, 1890 cases of dengue fever diagnosed by 88.3%., 5 cases of dengue hemorrhagic fever and 1 cases of dengue shock syndrome, 1262 cases of dengue fever were diagnosed according to the diagnostic criteria of WHO2009, and the diagnosis was associated with early warning. In 496 cases of dengue fever, 138 patients with severe dengue fever were diagnosed with severe dengue fever, 18 cases (13%) appeared shock, 6 cases (4.3%) had fluid exudation and respiratory depression, 77 cases of severe hemorrhage (55.8%) appeared, 5 cases (3.6%) appeared alanine aminotransferase or gluten transaminase higher than 1000U/L (3.6%) and 4 cases of consciousness disorder (2.9%) appeared. There were 31 cases (22.5%) with myocarditis and 11 cases (8%) with renal insufficiency.
2. of all the cases, 634 had severe early warning signs. The most frequent severe early warning signs were severe fatigue (28.5%), liquid exudation (15.7%) and skin mucous hemorrhage (27.1%), and WS with a specificity of more than 90% including abdominal pain (97.3%), liver enlargement (99.8%), and thrombocytopenia with elevated hematocrit (99.5%);
3, the first case of our report is that the first case of severe dengue fever in China is a 68 year old woman who has a history of diabetes and hypertension for many years. After this onset, fever, fatigue, headache, joint pain, skin ecchymosis and hemorrhage in the digestive tract appear. The damage of liver and kidney function was obvious, albumin decreased, and the gallbladder wall thickening was found by B ultrasonic examination.
4, virological detection showed that the dengue virus of this critically ill patient was DENV-1, belonging to genotype I and the highest homology with DENV-1 in Southeast Asian endemic area.
5, serological examination showed that the critically ill patient was the two infection of dengue virus. The dengue virus was first infected with DENV-2..
conclusion
1. of the 1896 patients in this group, 138 cases were diagnosed with severe dengue fever, which was more consistent with the severity of clinical manifestations. It was proved that the 2009 WHO dengue diagnostic guide was more suitable for clinical application in China. Abdominal pain, hepatomegaly, humoral exudation, increased hematocrit and reduced platelet count were specific early warning signs for severe dengue.
2. old age, female, diabetes and hypertension, and two infection of dengue virus are the main factors of dengue severe disease. The thickness of the gallbladder wall can be used as an indicator of early diagnosis of severe dengue fever.

【学位授予单位】：广州医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.8

【参考文献】