本文選題：重癥登革熱 + 回顧性分析��； 參考：《廣州醫(yī)科大學(xué)》2013年碩士論文

【摘要】：登革熱是一種急性發(fā)熱性傳染病，主要通過蚊媒傳播，它的病原體是登革病毒，該病毒有四種血清型（DENV1～4）。登革熱的臨床表現(xiàn)多種多樣，既可表現(xiàn)為普通發(fā)熱，也可發(fā)生致死性的重癥。登革出血熱和登革休克綜合癥等重癥病例造成每年約20,000例患者死亡，成為影響發(fā)展中國家公共健康的一種重要疾病。在我國，登革熱主要在沿海地區(qū)流行，其中以廣東省最為嚴(yán)重，廣東幾乎每年都有登革熱的報(bào)道。重癥登革熱病例病死率高，所以早期發(fā)現(xiàn)并對(duì)癥治療是救治重癥登革熱、降低病死率的關(guān)鍵。為了提高重癥登革熱的診斷成功率，世界衛(wèi)生組織（World Health Organization，WHO）于2009年發(fā)布了新的登革熱診治指南，將登革熱的臨床分型修改為登革熱和重癥登革熱兩大類型，其中登革熱又分為無預(yù)警征型和有預(yù)警征型，并將以下七個(gè)表現(xiàn)作為重癥預(yù)警征(Warningsigns,WS)，包括腹部疼痛或壓痛，持續(xù)性嘔吐，臨床血漿滲漏征，皮膚粘膜出血，極度乏力或煩躁，肝臟增大超過2厘米，伴隨紅細(xì)胞壓積升高的血小板迅速下降等。該分型方案已在全球多個(gè)流行地區(qū)的登革熱臨床診斷中得到了初步應(yīng)用，大多數(shù)研究認(rèn)為它能較好地指導(dǎo)臨床診治工作，但對(duì)其適用性仍存在爭議。在我國，這一新的分型方案尚未應(yīng)用于臨床，也未見相關(guān)的研究報(bào)道。因此，在我國人群中，探討重癥登革熱的臨床及實(shí)驗(yàn)室預(yù)警指標(biāo)，對(duì)于制定適用于我國患者的登革熱診治方案、提高登革熱的診治水平具有重要意義，同時(shí)也將為WHO發(fā)表的新版登革熱診治指南提供有益的補(bǔ)充。迄今為止，登革病毒感染引發(fā)重癥的原因尚不清楚，大量研究推測其與患者的年齡、性別和基礎(chǔ)疾病等宿主因素有關(guān)。此外，異型登革病毒的二次感染也可能是導(dǎo)致重癥登革熱的重要原因。從臨床資料、血清學(xué)和病毒學(xué)三個(gè)方面系統(tǒng)分析重癥登革熱患者病例,將為探尋重癥登革熱的發(fā)病機(jī)制和影響因素提供可靠的依據(jù)。 研究目的 1、總結(jié)我國登革熱的臨床及實(shí)驗(yàn)室特征，探討重癥登革熱預(yù)警指標(biāo)及2009年版的WHO登革熱診斷標(biāo)準(zhǔn)在我國的適用性; 2、分析我國首例重癥登革熱病例的臨床及病原學(xué)特征，初步揭示重癥登革熱的發(fā)病機(jī)制和影響因素。 研究方法 1、回顧性分析1990～2012年廣州市第八人民醫(yī)院收治的登革熱患者的臨床及實(shí)驗(yàn)室資料,得到的數(shù)據(jù)用臨床信息數(shù)據(jù)分析管理系統(tǒng)進(jìn)行處理，并統(tǒng)計(jì)分析； 2、回顧性分析一例重癥登革熱病例的臨床及實(shí)驗(yàn)室檢查的特征； 3、采用酶聯(lián)免疫法（ELISA）檢測該病例發(fā)病期和恢復(fù)期血清登革IgM和IgG抗體，并用蝕斑減少中和試驗(yàn)檢測其發(fā)病期及恢復(fù)期血清中針對(duì)不同血清型登革病毒的中和抗體水平。依據(jù)抗原原罪現(xiàn)象，確定該病人初次感染的登革病毒血清型； 4、采用WHO推薦的nested RT-PCR法擴(kuò)增該病例急性期血清中登革病毒的C-prM基因片段，確定其血清型。通過將C-prM基因序列在GenBank中進(jìn)行Blast比對(duì)，確定與該基因同源性最高的登革病毒序列，根據(jù)該序列，采用PCR DESIGN軟件設(shè)計(jì)擴(kuò)增E基因片段的引物，采用RT-PCR法擴(kuò)增該病例急性期血清中登革病毒的E基因片段，根據(jù)E基因序列，利用Neighbor-Joining法對(duì)該病毒株和其他29株DENV-1進(jìn)行系統(tǒng)進(jìn)化分析，確定該病毒的來源。 結(jié)果 1、1990年～2012年廣州市第八人民醫(yī)院共收治了1896例登革熱患者，其中年齡超過18歲者1647人，占88.3%。診斷為普通登革熱者1890例，診斷為登革出血熱者5例，診斷為登革休克綜合征者1例；按WHO2009診斷標(biāo)準(zhǔn)，診斷登革熱者1262例，，診斷為伴預(yù)警征的登革熱者496例，診斷為重癥登革熱者138人。138例重癥登革熱中，出現(xiàn)休克者18例（13.0%），出現(xiàn)體液滲出并呼吸抑制者6例（4.3%），出現(xiàn)嚴(yán)重出血者77例（55.8%），出現(xiàn)谷丙轉(zhuǎn)氨酶或谷草轉(zhuǎn)氨酶升高超過1000U/L者5例（3.6%），出現(xiàn)意識(shí)障礙者4例（2.9%），出現(xiàn)心肌炎者31例（22.5%），出現(xiàn)腎功能不全者11例（8.0%）。 2.全部病例中有634例次出現(xiàn)過重癥預(yù)警征，最常出現(xiàn)的重癥預(yù)警征為：重度乏力(28.5%)、液體滲出征(15.7%)和皮膚粘膜出血(27.1%)，特異性大于90%的WS包括腹痛(97.3%)、肝臟增大(99.8%)、伴隨紅細(xì)胞壓積升高的血小板減少(99.5%)； 3、我們此次報(bào)道的國內(nèi)首例確診重癥登革熱的病例是一位68歲的女性，她有糖尿病及高血壓病史多年，此次發(fā)病后，出現(xiàn)發(fā)熱、乏力、頭痛、全身關(guān)節(jié)痛，并出現(xiàn)皮膚注射部位瘀斑和消化道出血表現(xiàn)。檢查發(fā)現(xiàn)她的白細(xì)胞和血小板計(jì)數(shù)明顯下降，肝腎功能損害明顯，白蛋白降低，B超檢查發(fā)現(xiàn)膽囊壁增厚。 4、病毒學(xué)檢測結(jié)果顯示該重癥病人此次感染的登革病毒為DENV-1,屬于基因I型，與東南亞流行區(qū)的DENV-1同源性最高。 5、血清學(xué)檢測結(jié)果表明該重癥病人為登革病毒二次感染，其初次感染的登革病毒為DENV-2。 結(jié)論 1.在本組1896例病人中，符合重癥登革熱診斷者138例，與臨床表現(xiàn)的嚴(yán)重程度較相符，證明2009年WHO登革熱診斷指南較適合我國臨床應(yīng)用。腹痛、肝腫大、體液外滲征、紅細(xì)胞壓積升高伴血小板計(jì)數(shù)減少等是重癥登革熱的特異性預(yù)警征。 2.老年、女性、合并糖尿病和高血壓、以及登革病毒二次感染是本例登革熱發(fā)生重癥的主要因素。腹部彩色B超檢查膽囊壁厚度可能可以作為早期診斷重癥登革熱的指標(biāo)。
[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.

【學(xué)位授予單位】：廣州醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R512.8

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 宋韶芳;羅雷;景欽隆;楊智聰;;廣州市2001-2010年登革熱流行病學(xué)分析[J];熱帶醫(yī)學(xué)雜志;2012年02期

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