本文關(guān)鍵詞： 兒童 手足口病 高危因素 抗體　出處：《南方醫(yī)科大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景 手足口病(hand-foot-and-mouth disease, HPMD)是由多種腸道病毒引起的常見傳染病,以嬰幼兒發(fā)病為主,引發(fā)HFMD的病原體主要有腸道病毒71型(Enterovirus type71,簡(jiǎn)稱EV71)和柯薩奇病毒八組16型(Coxsakie virus group A type16,簡(jiǎn)稱CoxA16)。作為全球性傳染病,近年來HFMD已經(jīng)成為越來越威脅國內(nèi)外兒童健康的廣泛流行性疾病之一。HFMD輕癥患者常無臨床癥狀或僅有輕度不適,常表現(xiàn)為發(fā)熱、口腔皰疹、潰瘍,手、足和臀部出現(xiàn)斑丘疹、皰疹,多在1周內(nèi)痊愈,但是少數(shù)患者發(fā)展至重癥,常合并腦炎、腦膜炎、急性遲緩性麻痹、神經(jīng)源性肺水腫等嚴(yán)重并發(fā)癥,病情進(jìn)展迅速,甚至導(dǎo)致患兒死亡。目前重癥病例仍是HFMD研究的重點(diǎn)。因此,明確HFMD的高危因素,對(duì)于積極救治,改善預(yù)后和降低死亡率至關(guān)重要。 第一部分廣東省手足口病患兒臨床高危因素分析 目的總結(jié)手足口病的臨床特點(diǎn),探討重癥手足口病的高危因素。 方法以2008年4月至2011年12月本院收治的1204例HFMD患者為研究對(duì)象,其中男性806例(占66.86%),女性398例(占33.14%)。年齡3個(gè)月至14歲,平均2.25歲。本研究先描述HFMD患者在月份、年齡、性別等方面的分布情況,繼而依據(jù)《腸道病毒(EV71)感染診療指南(2010年版)》,將上述病人分為輕癥HFMD病例1156例(占96.01%)及重癥HFMD病例48例(占3.99%)。觀察HFMD患者的性別、年齡、發(fā)熱持續(xù)時(shí)間、熱峰、出疹時(shí)間、出疹部位及程度、精神、肢端溫度,有無流涕、驚跳、抽搐、意識(shí)改變、呼吸困難、嘔吐、腹脹,實(shí)驗(yàn)室定期檢測(cè)患者血常規(guī)、肝功能和心肌酶,必要時(shí)行胸片、心電圖、頭顱CT或磁共振檢查,應(yīng)用2009年5月衛(wèi)生部制定的《手足口病個(gè)案調(diào)查表》詳細(xì)記錄以上參數(shù)。對(duì)患者病情反復(fù)評(píng)估,明確患者病情變化情況。實(shí)時(shí)熒光定量PCR (RT-PCR)檢測(cè)腸道病毒通用型(EV)、EV71型不(?)CoxA16型核酸作病原體的測(cè)定。將HFMD患者的臨床癥狀、體征和檢驗(yàn)結(jié)果進(jìn)行分級(jí),結(jié)合EV71(?)CoxA16檢測(cè)陽性的HFMD患者病情的輕重給予單因素分析及多因素Logistic回歸分析。 結(jié)果 1.流行病學(xué)資料分析 2008年4月～2011年12月我院收治HFMD病例1204例,各年發(fā)病率的變化差異無統(tǒng)計(jì)學(xué)意義(P0.05)。4年中HFMD發(fā)病高峰均出現(xiàn)在每年的4-11月,低谷出現(xiàn)在12-3月份。男性患者806例(占66.94%),女性患者398例(占33.06%),男女性別比為2.03：1,各年度HFMD患者性別分布無明顯統(tǒng)計(jì)學(xué)差異(P0.05)。通過年齡分布進(jìn)行分析,最小的發(fā)病年齡是2個(gè)月,最大的發(fā)病年齡14歲。其中≤3歲943例(占78.32%),發(fā)病3且≤7歲235例(占19.51%),7歲26例(占2.16%)。2008年4月～2011年12月我院收治HFMD病例中,實(shí)時(shí)熒光定量PCR(RT-PCR)檢測(cè)陽性率以EV最高,其次為EV71,CoxA16排列第三位。EV71及CoxA16各年發(fā)病率的變化差異無統(tǒng)計(jì)學(xué)意義(P0.05)。各年度HFMD患者病情嚴(yán)重程度及性別分布無統(tǒng)計(jì)學(xué)差異(P0.05) 2.臨床資料分析 分析各年度HFMD患者一般性別、年齡、發(fā)病癥狀的分布差異。在所選取的觀察指標(biāo)中,年齡、發(fā)熱時(shí)間、熱峰、口腔粘膜皮疹、咳嗽、驚跳、意識(shí)改變、精神差均有統(tǒng)計(jì)學(xué)顯著性差異(P0.05)；性別、皮疹(手、足、臀)、流涕、抽搐、肢端溫度、呼吸困難、嘔吐、腹脹均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。把2008年4月～2011年12月我院收治1204例HFMD患者依據(jù)病情嚴(yán)重程度分為輕癥及重癥后,對(duì)其癥狀及發(fā)病早期(≤3天)查血常規(guī)及血生化檢驗(yàn)結(jié)果作單因素分析。其中發(fā)熱時(shí)間、臀部皮疹、驚跳、抽搐、意識(shí)改變、精神差、肢端溫度、呼吸困難、嘔吐、腹脹、發(fā)病早期(≤3天)Dbil值有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。一般情況及癥狀方面,年齡、起病到就診的間隔時(shí)間(天)、熱峰、皮疹(手、足、口)、咳嗽、流涕均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05),實(shí)驗(yàn)室指標(biāo)中,入院查WBC、PLT、GLU、ALT、AST、Tbil、Ibil、GGT、CK、CK_MB、 LDH_L、HBDH、HSCRP、PT、APTT、Fg、 PCT_F無顯著的統(tǒng)計(jì)學(xué)差異(P0.05)。采用logistic回歸的LR法對(duì)其癥狀及檢驗(yàn)結(jié)果作多因素分析,可知HFMD病情提示重癥的早期預(yù)警指標(biāo)為：驚跳、精神差、抽搐、嘔吐、發(fā)病早期(≤3天)WBC升高和Dbil升高。 3.HFMD患者感染EV71(?)臨床資料分析 把2008年4月～2011年12月我院收治240例病原體檢測(cè)EV71陽性的HFMD輕癥患者與重癥患者對(duì)比,對(duì)其癥狀及發(fā)病早期(≤3天)的血常規(guī)及血生化檢驗(yàn)結(jié)果作兩獨(dú)立樣本檢驗(yàn)。癥狀方面,肢端涼、嘔吐、腹脹、驚跳、意識(shí)改變、精神差、發(fā)熱持續(xù)時(shí)間(3天)有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)；檢驗(yàn)結(jié)果方面,發(fā)病早期(≤3天)查WBC值有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。而性別、年齡、皮疹(手、足、臀、口)、熱峰、咳嗽、流涕、呼吸困難、抽搐、起病到就診的間隔時(shí)間(天),以及入院檢驗(yàn)項(xiàng)目PLT、AST、CK_MB、HSCRP、PCT_F、GLU、 ALT、Tbil、Ibil、GGT、CK、LDH_L、HBDH、PT、APTT、Fg均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。采用logistic回歸的LR法對(duì)感染EV71的HFMD輕癥及重癥患者癥狀與檢驗(yàn)結(jié)果作多因素分析。結(jié)果顯示HFMD患者感染EV71提示重癥的高危因素為：咳嗽、驚跳、精神差。 4. HFMD患者感染CoxA16的臨床資料分析 把2008年4月～2011年12月我院收治82例病原體檢測(cè)示CoxA16陽性中輕癥與重癥患者作對(duì)比,對(duì)其癥狀及入院時(shí)所查血常規(guī)及血生化檢驗(yàn)結(jié)果作兩獨(dú)立樣本秩和檢驗(yàn)。癥狀方面,起病到就診的間隔時(shí)間(天)、抽搐有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)；檢驗(yàn)結(jié)果方面,發(fā)病早期(≤3天)查CK_MB值有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。而性別、年齡、發(fā)熱時(shí)間、熱峰、皮疹(手、足、臀、口)、咳嗽、流涕、驚跳、抽搐、意識(shí)改變、精神差、肢端溫度、呼吸困難、嘔吐、腹脹癥狀和發(fā)病早期(≤3天)查WBC、PLT、AST、HSCRP、GLU、ALT、Tbil、 Dbil、Ibil、GGT、CK、LDH_L、HBDH、PT、APTT、Fg、PCT_F均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。采用logistic回歸的LR法上述病人癥狀和檢驗(yàn)結(jié)果作多因素分析。統(tǒng)計(jì)結(jié)果提示抽搐為HFMD患者感染CoxA16為重癥病例的預(yù)警指標(biāo)。 結(jié)論HFMD以夏秋季為發(fā)病高峰季節(jié),主要易感人群為2.25～2.5歲幼兒,病原體以EV及EV71為主。EV71病毒是重癥HFMD患者及導(dǎo)致患兒死亡的主要病原體。經(jīng)單因素統(tǒng)計(jì)學(xué)分析,以下指標(biāo)在輕癥和重癥患者中具有顯著性差異(P0.05)：嘔吐、腹脹、肢端涼、呼吸困難、驚跳、抽搐、意識(shí)改變、精神差、發(fā)熱持續(xù)時(shí)間(3天)、臀部有皮疹和發(fā)病早期(≤3天)Dbil升高。經(jīng)多因素回歸分析,以下指標(biāo)為重癥病例的高危因素：驚跳、精神差、抽搐、嘔吐、發(fā)病早期(≤3天)WBC升高和Dbil升高。經(jīng)單因素統(tǒng)計(jì)學(xué)分析,以下指標(biāo)在EV71陽性輕癥和重癥患者中具有顯著性差異(P0.05)：肢端涼、嘔吐、腹脹、驚跳、意識(shí)改變、精神差、發(fā)熱持續(xù)時(shí)間(3天)。經(jīng)多因素回歸分析,以下指標(biāo)為EV71陽性HFMD重癥病例的高危因素：咳嗽、驚跳、精神差。經(jīng)單因素統(tǒng)計(jì)學(xué)分析,以下指標(biāo)在CoxA16陽性輕癥和重癥患者中具有顯著性差異(P0.05)：抽搐、起病到就診間隔天數(shù)(3天)。經(jīng)多因素回歸分析,以下指標(biāo)為CoxA16陽性HFMD重癥病例的高危因素：抽搐。 第二部分廣東省手足口病患兒病毒抗體研究 目的探討EV71-IgG對(duì)復(fù)發(fā)病例是否有保護(hù)作用(EV71-IgG) 方法以2008年4月至2012年3月本院收治的1209例患者中,抽取26例HFMD復(fù)發(fā)患者為研究對(duì)象,隨機(jī)抽取36例同期在本院HFMD首發(fā)患者設(shè)入對(duì)照組。26例HFMD復(fù)發(fā)患者中,男性17例(占65.38%),女性9例(占34.62%)；年齡3個(gè)月至4.5歲,平均2.22歲。36例首發(fā)HFMD患者中,男性24例(占66.67%),女性12例(占33.33%);年齡9個(gè)月至6歲,平均2.76歲。根據(jù)醫(yī)院設(shè)計(jì)《2010年門診手足口病人回訪記錄表》,記錄患兒一般情況、生命體征、呼吸系統(tǒng)、心血管系統(tǒng)、神經(jīng)系統(tǒng)癥狀及體征。對(duì)比急性期肛拭子EV71檢測(cè)結(jié)果與恢復(fù)期EV71-IgG生成情況。應(yīng)用SPSS13.0統(tǒng)計(jì)軟件包處理數(shù)據(jù),以x2檢驗(yàn)比較,P0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果從2008年4月至2012年3月本院收治的1209例患者中,抽取26例HFMD復(fù)發(fā)患者為研究對(duì)象,與首次獲得的患者做對(duì)照,對(duì)其癥狀及發(fā)病早期(≤3天)所查血常規(guī)及血生化檢驗(yàn)結(jié)果作t檢驗(yàn)。癥狀方面,年齡、發(fā)熱持續(xù)時(shí)間、熱峰、起病到就診的間隔時(shí)間(天)均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。對(duì)首發(fā)及復(fù)發(fā)HFMD患者做臨床癥狀的單因素分析,可見皮疹(手、足、口、臀)、咳嗽、流涕、驚跳、抽搐、精神差、呼吸困難、嘔吐、腹脹均無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。對(duì)首發(fā)及復(fù)發(fā)HFMD患者入院檢驗(yàn)結(jié)果做單因素分析,可見Cr、Glu有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。而WBC、LYM、GRAN、MONO、RBC、Hb、PIT、 K、Na、Cl、Ca、Urea、ALT、AST、Tbil、Dbil、Ibil、GGT、CK、CK_MB、LDH_L HBDH、HSCRP、PT、APTT、Fg、PCT_F無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。對(duì)首發(fā)及復(fù)發(fā)HFMD患者出院檢驗(yàn)結(jié)果做單因素分析,可見Na、ALT有統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。而WBC、LYM、GRAN、MONO、RBC、Hb、PLT、K、Cl、Ca、Urea、 AST、Tbil、Dbil、Ibil、GGT、CK、CK_MB、LDH_L、HBDH、HSCr、GluCRP、PT、 APTT、Fg、 PCT_F無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。分析首發(fā)及復(fù)發(fā)HFMD患者復(fù)發(fā)與首發(fā)手足口病患者急性期EV71核酸檢測(cè)與恢復(fù)期EV71-IgG檢測(cè)水平,提示急性期肛拭子檢測(cè)EV71陽性患兒是否復(fù)發(fā)與機(jī)體產(chǎn)生EV71-IgG無統(tǒng)計(jì)學(xué)顯著的差異(P0.05)。 結(jié)論EV71-IgG抗體對(duì)HFMD患者無保護(hù)作用,即IgG陽性患者也會(huì)復(fù)發(fā)。HFMD患者的EV71與其他病原學(xué)之間無交叉抗原性。
[Abstract]:Research background
Foot and mouth disease (hand-foot-and-mouth disease HPMD) is a common infectious disease caused by a variety of intestinal virus, mainly in infants, HFMD are the main pathogens caused by enterovirus 71 (Enterovirus type71, referred to as EV71) and Coxsackie virus type eight group 16 (Coxsakie virus group A type16, referred to as CoxA16) as a global epidemic. In recent years, HFMD has become more and more threat to children's health at home and abroad widely epidemic of.HFMD patients with mild and usually asymptomatic or only mild discomfort, often manifested as fever, oral herpes, ulcer, hand, foot and buttocks rash, herpes, cured in 1 weeks, but a minority of patients develop to severe, often associated with meningitis, encephalitis, acute flaccid paralysis, severe complications of neurogenic pulmonary edema, rapid progression, and even lead to death in children with severe cases. At present, HFMD is still on Therefore, it is essential to identify the high risk factors of HFMD for positive treatment, improvement of prognosis and reduction of mortality.
The first part analysis of the high risk factors for children with hand foot and mouth disease in Guangdong
Objective to summarize the clinical characteristics of hand foot and mouth disease (HFMD) and to explore the high risk factors of severe hand foot and mouth disease.
Methods 1204 cases of HFMD patients from April 2008 to December 2011 in our hospital were selected as the research object, including 806 cases of male (66.86%), 398 cases were female (33.14%). The age ranged from 3 months to 14 years, average 2.25 years old. This study first describes HFMD patients in July, age distribution, gender and other aspects. Then on the basis of "intestinal virus (EV71) infection diagnosis and treatment guidelines (2010 Edition) >, the patients were divided into mild HFMD cases in 1156 cases (96.01%) and severe HFMD were 48 cases (3.99%). HFMD was observed in patients with sex, age, duration of fever, rash and heat peak, time, location and rash the degree of the spirit, there is no acral temperature, runny nose, startle, convulsions, consciousness changes, difficulty in breathing, vomiting, abdominal distension, regular laboratory detection of blood routine test, liver function and myocardial enzymes, if necessary, chest X-ray, ECG, head CT or magnetic resonance imaging applications, in May 2009 the Ministry of health to develop a" hand foot and mouth disease The case with the above parameters. The questionnaire > record repeated assessment of patients'condition, clear changes in patient condition. Real time fluorescence quantitative PCR (RT-PCR) detection of enterovirus universal type (EV), type EV71 (?) CoxA16 type nucleic acid for determination of pathogens. The clinical symptoms of patients with HFMD, signs and test results were graded. With EV71 (?) CoxA16 positive HFMD patients were given the severity of the Logistic regression analysis of single factor and multi factors analysis.
Result
Analysis of 1. epidemiological data
From April 2008 to December 2011 in our hospital 1204 cases of HFMD patients, there was no significant difference in the incidence of change each year (P0.05).4 in HFMD peak appeared in the year of 4-11 months, the trough appeared in 12-3 months. 806 cases of male patients (66.94%), 398 cases of female patients (33.06%), gender ratio of 2.03:1, HFMD in each year were no statistically significant differences in gender distribution (P0.05). Through the analysis of the age distribution, the minimum age is 2 months, the maximum age of 14 years. Among them 943 patients less than 3 years (78.32%), the incidence of 3 and less than 7 years old in 235 cases (19.51%). At the age of 7 in 26 cases (2.16%).2008 years from April to December 2011 in our hospital were HFMD cases, real-time fluorescence quantitative PCR (RT-PCR) positive rate was the highest in EV, followed by EV71, CoxA16,.EV71 and CoxA16 ranked third to change each year the incidence of no significant difference (P0.05) of HFMD in each year. Patients There was no statistical difference between the severity of the disease and the distribution of sex (P0.05)
2. clinical data analysis
Analysis of the annual HFMD patients with gender, age, distribution of symptoms. In the observation of the selected indicators, age, duration of fever, heat peak, oral mucosa rash, cough, startle, change of consciousness, the spirit of difference had significant difference (P0.05); sex, (hand, foot, hip.), runny nose, convulsions, limb temperature, difficulty breathing, vomiting, no statistically significant difference (P0.05). The abdominal distension from April 2008 to December 2011 in our hospital 1204 cases of HFMD patients according to the severity of the disease is divided into mild and severe, the symptoms and the incidence of early (within 3 days) for single factor analysis. Blood routine and biochemical test results. The heating time, the buttocks rash, startle, convulsions, consciousness, spirit, acral temperature, difficulty breathing, vomiting, abdominal distension, early onset (within 3 days) Dbil values were statistically significant differences (P0.05). The general condition and symptoms, age, The time interval from onset to peak (day), heat rash, (hand, foot, mouth), cough, there were no differences statistically significant (P0.05), runny nose, laboratory index, admission check WBC, PLT, GLU, ALT, AST, Tbil, Ibil, GGT, CK, CK_MB, LDH_L, HBDH HSCRP, PT, APTT, Fg, PCT_F, no statistically significant difference (P0.05). Multivariate LR analysis method using logistic regression of the symptoms and test results, the early warning indicators of severe HFMD disease that is: poor spirit, startle, convulsions, vomiting, the incidence of early (within 3 days) WBC increased and Dbil increased.
Analysis of the clinical data of EV71 (?) infection in 3.HFMD patients
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