广东省手足口病患儿临床高危因素分析和病毒抗体研究

发布时间：2018-01-25 23:16

  本文关键词： 儿童 手足口病 高危因素 抗体　出处：《南方医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：研究背景 手足口病(hand-foot-and-mouth disease, HPMD)是由多种肠道病毒引起的常见传染病,以婴幼儿发病为主,引发HFMD的病原体主要有肠道病毒71型(Enterovirus type71,简称EV71)和柯萨奇病毒八组16型(Coxsakie virus group A type16,简称CoxA16)。作为全球性传染病,近年来HFMD已经成为越来越威胁国内外儿童健康的广泛流行性疾病之一。HFMD轻症患者常无临床症状或仅有轻度不适,常表现为发热、口腔疱疹、溃疡,手、足和臀部出现斑丘疹、疱疹,多在1周内痊愈,但是少数患者发展至重症,常合并脑炎、脑膜炎、急性迟缓性麻痹、神经源性肺水肿等严重并发症,病情进展迅速,甚至导致患儿死亡。目前重症病例仍是HFMD研究的重点。因此,明确HFMD的高危因素,对于积极救治,改善预后和降低死亡率至关重要。 第一部分广东省手足口病患儿临床高危因素分析 目的总结手足口病的临床特点,探讨重症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患者为研究对象,其中男性806例(占66.86%),女性398例(占33.14%)。年龄3个月至14岁,平均2.25岁。本研究先描述HFMD患者在月份、年龄、性别等方面的分布情况,继而依据《肠道病毒(EV71)感染诊疗指南(2010年版)》,将上述病人分为轻症HFMD病例1156例(占96.01%)及重症HFMD病例48例(占3.99%)。观察HFMD患者的性别、年龄、发热持续时间、热峰、出疹时间、出疹部位及程度、精神、肢端温度,有无流涕、惊跳、抽搐、意识改变、呼吸困难、呕吐、腹胀,实验室定期检测患者血常规、肝功能和心肌酶,必要时行胸片、心电图、头颅CT或磁共振检查,应用2009年5月卫生部制定的《手足口病个案调查表》详细记录以上参数。对患者病情反复评估,明确患者病情变化情况。实时荧光定量PCR (RT-PCR)检测肠道病毒通用型(EV)、EV71型不(?)CoxA16型核酸作病原体的测定。将HFMD患者的临床症状、体征和检验结果进行分级,结合EV71(?)CoxA16检测阳性的HFMD患者病情的轻重给予单因素分析及多因素Logistic回归分析。 结果 1.流行病学资料分析 2008年4月～2011年12月我院收治HFMD病例1204例,各年发病率的变化差异无统计学意义(P0.05)。4年中HFMD发病高峰均出现在每年的4-11月,低谷出现在12-3月份。男性患者806例(占66.94%),女性患者398例(占33.06%),男女性别比为2.03：1,各年度HFMD患者性别分布无明显统计学差异(P0.05)。通过年龄分布进行分析,最小的发病年龄是2个月,最大的发病年龄14岁。其中≤3岁943例(占78.32%),发病3且≤7岁235例(占19.51%),7岁26例(占2.16%)。2008年4月～2011年12月我院收治HFMD病例中,实时荧光定量PCR(RT-PCR)检测阳性率以EV最高,其次为EV71,CoxA16排列第三位。EV71及CoxA16各年发病率的变化差异无统计学意义(P0.05)。各年度HFMD患者病情严重程度及性别分布无统计学差异(P0.05) 2.临床资料分析 分析各年度HFMD患者一般性别、年龄、发病症状的分布差异。在所选取的观察指标中,年龄、发热时间、热峰、口腔粘膜皮疹、咳嗽、惊跳、意识改变、精神差均有统计学显著性差异(P0.05)；性别、皮疹(手、足、臀)、流涕、抽搐、肢端温度、呼吸困难、呕吐、腹胀均无统计学显著的差异(P0.05)。把2008年4月～2011年12月我院收治1204例HFMD患者依据病情严重程度分为轻症及重症后,对其症状及发病早期(≤3天)查血常规及血生化检验结果作单因素分析。其中发热时间、臀部皮疹、惊跳、抽搐、意识改变、精神差、肢端温度、呼吸困难、呕吐、腹胀、发病早期(≤3天)Dbil值有统计学显著的差异(P0.05)。一般情况及症状方面,年龄、起病到就诊的间隔时间(天)、热峰、皮疹(手、足、口)、咳嗽、流涕均无统计学显著的差异(P0.05),实验室指标中,入院查WBC、PLT、GLU、ALT、AST、Tbil、Ibil、GGT、CK、CK_MB、 LDH_L、HBDH、HSCRP、PT、APTT、Fg、 PCT_F无显著的统计学差异(P0.05)。采用logistic回归的LR法对其症状及检验结果作多因素分析,可知HFMD病情提示重症的早期预警指标为：惊跳、精神差、抽搐、呕吐、发病早期(≤3天)WBC升高和Dbil升高。 3.HFMD患者感染EV71(?)临床资料分析 把2008年4月～2011年12月我院收治240例病原体检测EV71阳性的HFMD轻症患者与重症患者对比,对其症状及发病早期(≤3天)的血常规及血生化检验结果作两独立样本检验。症状方面,肢端凉、呕吐、腹胀、惊跳、意识改变、精神差、发热持续时间(3天)有统计学显著的差异(P0.05)；检验结果方面,发病早期(≤3天)查WBC值有统计学显著的差异(P0.05)。而性别、年龄、皮疹(手、足、臀、口)、热峰、咳嗽、流涕、呼吸困难、抽搐、起病到就诊的间隔时间(天),以及入院检验项目PLT、AST、CK_MB、HSCRP、PCT_F、GLU、 ALT、Tbil、Ibil、GGT、CK、LDH_L、HBDH、PT、APTT、Fg均无统计学显著的差异(P0.05)。采用logistic回归的LR法对感染EV71的HFMD轻症及重症患者症状与检验结果作多因素分析。结果显示HFMD患者感染EV71提示重症的高危因素为：咳嗽、惊跳、精神差。 4. HFMD患者感染CoxA16的临床资料分析 把2008年4月～2011年12月我院收治82例病原体检测示CoxA16阳性中轻症与重症患者作对比,对其症状及入院时所查血常规及血生化检验结果作两独立样本秩和检验。症状方面,起病到就诊的间隔时间(天)、抽搐有统计学显著的差异(P0.05)；检验结果方面,发病早期(≤3天)查CK_MB值有统计学显著的差异(P0.05)。而性别、年龄、发热时间、热峰、皮疹(手、足、臀、口)、咳嗽、流涕、惊跳、抽搐、意识改变、精神差、肢端温度、呼吸困难、呕吐、腹胀症状和发病早期(≤3天)查WBC、PLT、AST、HSCRP、GLU、ALT、Tbil、 Dbil、Ibil、GGT、CK、LDH_L、HBDH、PT、APTT、Fg、PCT_F均无统计学显著的差异(P0.05)。采用logistic回归的LR法上述病人症状和检验结果作多因素分析。统计结果提示抽搐为HFMD患者感染CoxA16为重症病例的预警指标。 结论HFMD以夏秋季为发病高峰季节,主要易感人群为2.25～2.5岁幼儿,病原体以EV及EV71为主。EV71病毒是重症HFMD患者及导致患儿死亡的主要病原体。经单因素统计学分析,以下指标在轻症和重症患者中具有显著性差异(P0.05)：呕吐、腹胀、肢端凉、呼吸困难、惊跳、抽搐、意识改变、精神差、发热持续时间(3天)、臀部有皮疹和发病早期(≤3天)Dbil升高。经多因素回归分析,以下指标为重症病例的高危因素：惊跳、精神差、抽搐、呕吐、发病早期(≤3天)WBC升高和Dbil升高。经单因素统计学分析,以下指标在EV71阳性轻症和重症患者中具有显著性差异(P0.05)：肢端凉、呕吐、腹胀、惊跳、意识改变、精神差、发热持续时间(3天)。经多因素回归分析,以下指标为EV71阳性HFMD重症病例的高危因素：咳嗽、惊跳、精神差。经单因素统计学分析,以下指标在CoxA16阳性轻症和重症患者中具有显著性差异(P0.05)：抽搐、起病到就诊间隔天数(3天)。经多因素回归分析,以下指标为CoxA16阳性HFMD重症病例的高危因素：抽搐。 第二部分广东省手足口病患儿病毒抗体研究 目的探讨EV71-IgG对复发病例是否有保护作用(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复发患者为研究对象,随机抽取36例同期在本院HFMD首发患者设入对照组。26例HFMD复发患者中,男性17例(占65.38%),女性9例(占34.62%)；年龄3个月至4.5岁,平均2.22岁。36例首发HFMD患者中,男性24例(占66.67%),女性12例(占33.33%);年龄9个月至6岁,平均2.76岁。根据医院设计《2010年门诊手足口病人回访记录表》,记录患儿一般情况、生命体征、呼吸系统、心血管系统、神经系统症状及体征。对比急性期肛拭子EV71检测结果与恢复期EV71-IgG生成情况。应用SPSS13.0统计软件包处理数据,以x2检验比较,P0.05为差异有统计学意义。 结果从2008年4月至2012年3月本院收治的1209例患者中,抽取26例HFMD复发患者为研究对象,与首次获得的患者做对照,对其症状及发病早期(≤3天)所查血常规及血生化检验结果作t检验。症状方面,年龄、发热持续时间、热峰、起病到就诊的间隔时间(天)均无统计学显著的差异(P0.05)。对首发及复发HFMD患者做临床症状的单因素分析,可见皮疹(手、足、口、臀)、咳嗽、流涕、惊跳、抽搐、精神差、呼吸困难、呕吐、腹胀均无统计学显著的差异(P0.05)。对首发及复发HFMD患者入院检验结果做单因素分析,可见Cr、Glu有统计学显著的差异(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无统计学显著的差异(P0.05)。对首发及复发HFMD患者出院检验结果做单因素分析,可见Na、ALT有统计学显著的差异(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无统计学显著的差异(P0.05)。分析首发及复发HFMD患者复发与首发手足口病患者急性期EV71核酸检测与恢复期EV71-IgG检测水平,提示急性期肛拭子检测EV71阳性患儿是否复发与机体产生EV71-IgG无统计学显著的差异(P0.05)。 结论EV71-IgG抗体对HFMD患者无保护作用,即IgG阳性患者也会复发。HFMD患者的EV71与其他病原学之间无交叉抗原性。
[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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