手足口病病原体流行特征分析及临床意义

Objective To investigate the epidemic characteristics of etiological agents in children with hand, foot and mouth disease (HFMD) and analyze the differences between the severe and mild cases with HFMD seen from 2008 to 2009 in the Children's Hospital Methods A total of 154 patients with HFMD were enrolled from May 2008 to September 2008 and from May 2009 to September 2009, including 28 severe HFMD patients. Data from 80 cases with suspected herpangina were collected as control. Enterovirus universal type, enterovirus type 71 (EV71) and coxsackie virus group A 16 (CA16) were detected by realtime RT-PCR respoctively. Results The positive rate of enterovirus universal type in the 154 patients with HFMD was 81.82% (126/154). EV71 positive rate in these 126 patients with enterovirus universal type infection was 57.14% (72/126). The positive rate of enterovirus universal type in the 80 cases with suspected herpangina was 68.75% (55/80). There was no EV71 infection in these 80 cases with suspected herpangina. EV71 infection was mainly popular in 2008. Both EV71 and CA16 were prevalent in 2009. The epidemic characteristics of enterovirus infection with HFMD between 2008 and 2009 had significant differences (X2 = 23.50, P = 0.000) ( P ＜ O.01 ). The epidemic characteristics of enterovirus infection between severe and mild HFMD patients also had significant differences (X2 = 29.85, P ＜ O. 01). There were 28 cases with severe HFMD, in whom the EV71 positive rate was 92.86% (26/28). EV71 positive rate in the mild HFMD was 36.51% (46/126) (X2 =29.22, P ＜0.01). There was no significant difference in the gender ( X2 = 0.135, P = 0.714) and virus load (t = 0.141, P = 0.889) between the mild and severe HFMD cases. But the age of mild and severe HFMD showed a significant difference ( t = 2.926, P =O.009). Patients who were less than 2 years of age had a proportion of 88.89% (8/9) with severe HFMD.The mean age of mild HFMD patients was 3.19 years. Conclusion HFMD showed different epidemic characteristics at different times of enterovirus infection. There was no significant difference in the gender and virus load between the mild and severe cases with HFMD. Children under 3 years of age with EV71 infection were at high risk for severe HFMD.     

手足口病病原体流行特征分析及临床意义

Objective To investigate the epidemic characteristics of etiological agents in children with hand, foot and mouth disease (HFMD) and analyze the differences between the severe and mild cases with HFMD seen from 2008 to 2009 in the Children's Hospital Methods A total of 154 patients with HFMD were enrolled from May 2008 to September 2008 and from May 2009 to September 2009, including 28 severe HFMD patients. Data from 80 cases with suspected herpangina were collected as control. Enterovirus universal type, enterovirus type 71 (EV71) and coxsackie virus group A 16 (CA16) were detected by realtime RT-PCR respoctively. Results The positive rate of enterovirus universal type in the 154 patients with HFMD was 81.82% (126/154). EV71 positive rate in these 126 patients with enterovirus universal type infection was 57.14% (72/126). The positive rate of enterovirus universal type in the 80 cases with suspected herpangina was 68.75% (55/80). There was no EV71 infection in these 80 cases with suspected herpangina. EV71 infection was mainly popular in 2008. Both EV71 and CA16 were prevalent in 2009. The epidemic characteristics of enterovirus infection with HFMD between 2008 and 2009 had significant differences (X2 = 23.50, P = 0.000) ( P ＜ O.01 ). The epidemic characteristics of enterovirus infection between severe and mild HFMD patients also had significant differences (X2 = 29.85, P ＜ O. 01). There were 28 cases with severe HFMD, in whom the EV71 positive rate was 92.86% (26/28). EV71 positive rate in the mild HFMD was 36.51% (46/126) (X2 =29.22, P ＜0.01). There was no significant difference in the gender ( X2 = 0.135, P = 0.714) and virus load (t = 0.141, P = 0.889) between the mild and severe HFMD cases. But the age of mild and severe HFMD showed a significant difference ( t = 2.926, P =O.009). Patients who were less than 2 years of age had a proportion of 88.89% (8/9) with severe HFMD.The mean age of mild HFMD patients was 3.19 years. Conclusion HFMD showed different epidemic characteristics at different times of enterovirus infection. There was no significant difference in the gender and virus load between the mild and severe cases with HFMD. Children under 3 years of age with EV71 infection were at high risk for severe HFMD.     

危重患儿血糖与胰岛素水平的临床分析

Objective To analyse the changes of blood glucose and insulin levels in children with critical illness,and to investigate the mechanism of hyperglycemia in critical illness.Methods Blood glucose and insulin levels were detected among 51 critically ill children hospitalized in our PICU from January to December,2007,which were compared with those of 15 healthy children.Results (1) All the patients had hyperglycemia after admission within 2Ah,septic shock patients showed the highest level with the maximum value of 27.30 mmol/L The dally mean blood glucose levels of the first 5 days after admission peaked on the admission day.(2) Within 24 h after admission,the blood insulin levels of patients with pulmonary infection,intracranial infection,septic shock and congenital heart disease were(17.65±16.85) mU/L,(13.45±7.33) mU/L,(16.24±12.41) mU/L,(6.75±3.22) mU/L respectively.The blood insulin levels of all the patients within the first 5 days after admission wrere higher than that of healthy children[(8.70±6.57) mU/L].According to blood glucose level on admission day,the patients were divided into normoglycemia and hyperglycemia group,and the blood insulin levels of the former and the letter were(5.44 ± 3.38) mU/L and (14.22±12.29) mU/L respectively.(3) The mean of PIM Ⅱscore of the patients averaged 12.96±16.82,and the mortality rate was 15.6%.The blood glucose level and the insulin level within 24 h after admission were(10.97±5.76) mmol/L and(49.46±90.35) mU/L in dead cases and(8.73±2.58) mmol/L and(11.91±11.24) mU/L for the survivals,and both the blood glucose level and insulin level had significant difference between the dead cases and survivals(P ＜0.05).(4) The scatter graphic analysis did not show significant linear relation between blood glucose and insulin,nor did it show significant linear relation between PIM Ⅱ and insulin levei,or blood glucose.Condusion Hyperglycemia and hyperinsulinemia are common in critical illness,which reflects indirectly the severity and prognosis of the disease.Hyperglycemia may be related to relative insulin insufficiency or insulin resistance;however,the definite relationship can not be confirmed until more reliable clinical data were available in the future.     

Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy

AIM: The mechanism of pulmonary oedema, a life-threatening manifestation of enterovirus 71 (EV71) encephalitis, is unclear. Our aim was to assess the relationship of proinflammatory cytokines to EV71-related pulmonary oedema. METHODS: Proinflammatory responses in 33 EV71 patients with various complications and 21 normal healthy children were measured using an enzyme-linked immunosorbent assay. RESULTS: EV71 patients with both encephalitis and pulmonary oedema were found to have much higher levels of blood interleukin-6 (IL-6) (947 +/- 1239 vs 4.9 +/- 3.1 pg/ml, p = 0.0003), tumour necrosis factor-alpha (TNF-alpha) (22.4 +/- 29.5 vs 5.3 +/- 1.0 pg/ml, p = 0.0035), interleukin Ibeta (IL-1beta) (48.4 +/- 85.2 vs 4.9 +/- 10.1 pg/ml, p = 0.01), white blood cell count (28.3 +/- 7.6 vs 15.5 +/- 6.8 10(9)/L, p > or = 0.0001) and blood glucose (501 +/- 186 vs 165 +/- 117 mg/dL, p = 0.0009) than patients with EV71 encephalitis alone. In fact, the cytokine levels in patients with encephalitis only or in those without complications were not significantly different from the levels found in normal children. The sensitivity, specificity, positive and negative predictive values of IL-6 > 70 pg/ml for EV71 encephalitis with pulmonary oedema were all 100%. CONCLUSION: Patients with EV71-related encephalitis combined with pulmonary oedema were found to have significantly elevated levels of proinflammatory cytokines and the best predictor for this complicated condition was found to be the level of serum IL-6.     

Predictors of unfavorable outcomes in enterovirus 71-related cardiopulmonary failure in children

BACKGROUND: Enterovirus 71 (EV71) can sometimes cause fatal or disabling diseases in children; therefore EV71-infected children with cardiopulmonary failure were investigated at Chang Gung Children's Hospital to discover the prognostic predictors. METHODS: We investigated 27 EV71-infected children with cardiopulmonary failure from May 2000 to September 2001 and analyzed their clinical data to find predictors associated with unfavorable outcomes of deaths or ventilator dependence. RESULTS: Of the 27 patients, 8 (30%) died and 10 (37%) were ventilator-dependent. Troponin I levels correlated most strongly with fatality, with 5 of the 6 children with troponin I levels >40 ng/ml dying (P = 0.001). Other factors correlated with fatality were cerebrospinal fluid white blood cell count > or =100/microL (P = 0.002) and initial systolic pressure < or =100 mm Hg (P = 0.05). Of the 19 survivors, 10 (53%) were left with central hypoventilation, dysphagia and/or limb weakness plus atrophy. The factors associated with ventilator dependence included higher inotrope equivalent (P < 0.001), duration of hypotension > or =40 hours, initial blood systolic pressure < or =100 mm Hg, positive EV71 isolation and age > or =12 months. CONCLUSIONS: Poor prognostic factors were related to cardiovascular and neurologic damage; therefore physicians may consider advanced cardiovascular support for EV71-infected children with cardiopulmonary failure.     

Sodium nitroprusside treatment of severe arterial hypertension in children.

Severe arterial hypertension in children constitutes a high-risk situation requiring rapid and effective therapy. We have assessed the clinical value of sodium nitroprusside as a rapidly acting antihypertensive agent. Twenty children admitted with hypertensive crises of renal origin were treated with intravenous infusion of sodium nitroprusside at an average rate of 1.4 mug/kg/min. Desired levels of blood pressure were reached in all patients within one to 20 minutes. Rapid improvement of cardiac failure was observed in all patients, and neurologic signs of distress disappeared in 16 of the 20 children within 24 to 48 hours of treatment, permitting substitution of oral medication. One patient died of cerebral hemorrhage without improvement of encephalopathy. There were no undesirable effects of therapy or deterioration of renal function in any patient.     

肠道病毒71型感染首发肺水肿与肺出血三例报告

目的 了解肠道病毒71型首发肺水肿或肺出血的暴发性致死性的临床特征.方法 回顾分析3例的临床表现,化验检查,诊断,治疗转归等.结果 此3例均死亡,病初仅有发热、呕吐等非特异性症状,均无手足口臀部皮疹,发病后1～2 d病情迅速恶化,突发口唇发绀,呼吸急促.3例均误诊,因考虑感染性休克而扩容.均未能早期认识肺出血,直至出现口鼻吐血性液、全身发绀等才行气管插管,气管内均见大量血性泡沫液.3例血糖显著升高和肌张力降低,2例心动过速,1例高血压.3例胸片双侧或单侧渗出性病变,心影不大,3例外周血白细胞均升高,3例咽拭子、气管分泌液和1例脑脊液样本均检测到肠道病毒71型.结论 婴幼儿首发肺水肿或肺出血患儿,符合肠道病毒71型感染特点,发生神经源性肺水肿或肺出血,急诊医生对该类疾病认识和处理不足.婴幼儿病初仅发热伴呕吐,数天后突发口唇发绀,呼吸急促,心动过速,高血压或低血压,肌张力低下,应高度怀疑该病,警惕肺水肿、肺出血.及时告知预后不良,扩容将迅速加剧病情恶化,应严格控制液体,早期气管插管正压通气,积极心功能支持.     

2002年上海儿童手足口病病例中肠道病毒71型和柯萨奇病毒A组16型的调查

目的对上海地区2002年4—6月儿童手足口病流行期间的手足口病患儿进行病原学调查。方法采集手足口病患儿的疱疹液、粪便、咽拭子进行病毒分离;分别用肠道病毒组合血清、肠道病毒71型（EV71）单价血清和柯萨奇病毒A组16型（CA16）单价血清对分离到的病毒进行中和试验定型;对不能定型的病毒株再分别用EV71和CA16的VP1基因的特异性引物进行RT-PCR鉴定。结果从72例患儿共采集102份标本,由其中67例患儿的91份标本分离到病毒;所有分离到的病毒株均不能用血清学方法进行定型;进一步经RT—PCR检测,58例为CA16,9例为EV71,二者之比为6．4：1;其中2例的EV71病毒株经中国疾病预防控制中心进行序列分析,认为属新的C4基因亚型;在EV71阳性病例中1例并发脑炎,出现抽搐、休克、昏迷、呼吸衰竭。结论从该组手足口病患儿检测到的主要病原是CA16和EV71;在上海地区首次报道与EV71感染相关的手足口病合并重症脑炎病例。     

白细胞介素-10基因多态性与儿童肠道病毒71型感染的相关性研究

目的 探讨白细胞介素-10（IL-10）基因位点-1082A/G、-819C/T和-592C/A多态性与IL-10水平及儿童肠道病毒71型（EV71）感染程度的关系。方法 选取EV71感染的手足口病患儿137例为研究对象,其中轻症组91例,重症组46例,另选取行健康体检儿童122例为健康对照组,采集临床数据。采用酶联免疫吸附试验（ELISA）检测血清IL-10水平。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术检测IL-10基因位点-1082A/G、-819C/T和-592C/A的多态性。结果 与健康对照组相比,EV71感染组患儿的-1082位点AA基因型频率和A等位基因频率更高（P < 0.05）。在EV71感染组中,重症组-1082位点AA基因型频率和A等位基因频率高于轻症组（P < 0.05）。两组间IL-10基因位点-819C/T和-592C/A多态性的分布比较差异均无统计学意义（P > 0.05）。重症组患儿血清IL-10水平明显高于轻症组和健康对照组（P < 0.05）。IL-10-1082 AA基因型、-819 TT基因型和-592 AA基因型与IL-10的低表达有关（P < 0.05）。在单倍型构建上,EV71感染组GCC单倍型的频率低于健康对照组（P < 0.05）。在EV71重症感染组中,ATA单倍型患儿的IL-10水平较其他单倍型显著降低,而GCC患儿的IL-10水平较其他单倍型显著升高（P < 0.05）;轻症组和健康对照组各单倍型间的IL-10水平比较差异无统计学意义（P > 0.05）。结论 IL-10基因多态性与IL-10表达水平及EV71感染严重程度有关。     

Noradrenaline use for septic shock in children: doses, routes of administration and complications

Aim: To report our 10 year experience with noradrenaline use in children with septic shock focusing on doses, routes of administration and complications. Methods: Retrospective single‐centre review of children with septic shock who received noradrenaline between 2000 and 2010. Results: We identified 144 children with septic shock treated with noradrenaline, in 22% as the first‐line drug. The median volume resuscitation before vasoactive agent administration was 50 mL/kg interquartile range [IQR: 30–70]. Mean doses of noradrenaline ranged from 0.5 ± 0.4 μg/kg per min (starting dose) to 2.5 ± 2.2 μg/kg per min (maximum dose). Noradrenaline was administered via peripheral venous access or intra‐osseous route in 19% of cases for a median duration of 3 h [IQR: 2–4] without any adverse effects. The use of noradrenaline increased over the study period. Mortality rate was 45% with a significant decrease over the study period. Adverse effects included arrhythmia in two children and hypertension in eight children. None of these arrhythmias required treatment and hypertension resolved with the noradrenaline dose reduction. Conclusion: Higher doses of noradrenaline than those suggested in the literature may be necessary to reverse hypotension and hypoperfusion. The use of noradrenaline through peripheral venous access or intra‐osseous route was safe, without any adverse effects.     

Critical management in patients with severe enterovirus 71 infection

OBJECTIVE: The aim of this study was to analyze clinical details occurring in children with severe enterovirus 71 (EV71) infection and synthesize the critical care experience for patients with severe EV71 infection. METHODS: A retrospective clinical, laboratory, and hemodynamic study was performed in a pediatric intensive care unit in a university hospital. From March 1998 to April 2000, seven consecutive pediatric patients with severe EV71 infection were retrospectively analyzed as the comparison group. From May 2000 to March 2003, eight consecutive patients with severe EV71 infection who had received the protocol therapy were enrolled as the study group. Detailed information about clinical treatment and pharmacological therapy was collected for comparison. RESULTS: The clinical presentations and laboratory findings between the comparison and the study groups were not significantly different. The amount of intravenous fluid in the first 24 h was significantly higher in the comparison group (9.2+/-5.0 vs 4.9+/-1.3 mL/kg per h). More patients in the study group received low doses of dopamine infusion, patients in the comparison group received more epinephrine, and none of them received milrinone. The acute-stage and long-term survival rates were higher in the study group (100% vs 43%, 87% vs 29%). CONCLUSION: Early cardiopulmonary support may prevent the vicious cycle of cardiopulmonary failure and improve the clinical outcome of severe EV71 infection. Milrinone may be the ideal inotropic agent for these patients. Echocardiography, a central line, and an arterial line could be an alternate method to replace direct intracardiac hemodynamic monitoring for guiding critical management.     

先天性心脏病术后感染性休克的诊疗特点

目的 总结婴幼儿先天性心脏病术后感染性休克的诊治特点.方法 对中国医学科学院阜外心血管病医院小儿心脏外科监护室在2006年6月至10月收治的422例心脏病术后病例进行回顾性研究.治疗方法 包括:(1) 液体快速扩容(5～10ml/kg),30min泵入,积极纠正酸中毒;(2) 常规应用多巴胺、多巴酚丁胺和米力农或硝酸甘油,必要时应用肾上腺素[0.05～0.5μg/(kg·min)];(3) 经上述处理,仍不能维持满意的血压时,加用去甲肾上腺素[0.2～0.5μg/(kg·min)],同时继续扩容;(4) 上述治疗1～2h仍不能纠正低血压或组织灌注不足时,加用垂体后叶素0.1～0.8U/h静脉泵入;(5) 继续输液:5～10ml/(kg·h),维持4～8h.结果 按照我中心自主提出的心脏体外循环术后感染性休克的诊断标准,14例患儿术后发生感染性休克.经过治疗,所有患儿的血压和组织灌注指标均明显好转.存活10例,死亡的4例患儿全部有外科原因.结论 先天性心脏病术后感染性休克的诊断有自身特点,结合心脏病特点抗休克治疗可取得较好效果,决定预后的关键是原发病的治疗情况.     

广州地区健康儿童肠道病毒71型抗体水平调查

目的 调查广州地区健康儿童肠道病毒71型抗体IgG（EV71-IgG）的水平,分析与EV71所致手足口病(HFMD)发病的关系。方法 以来源于广州市妇女儿童医疗中心（我院）中心实验室分离到的EV71 C4亚型标本,制备EV71诊断抗原,建立EV71-IgG抗体诊断试剂盒方法,并进行实验室评价。收集2010年1～3月在我院儿保科抽血进行常规保健检测的标本,筛选出无发热、无HFMD症状的健康儿童血清标本,检测EV71-IgG抗体。选取我院2010年全年门诊及住院HFMD患儿的咽拭子标本进行EV71特异性核酸检测。结果 ①本研究建立的试剂盒EV71-IgG抗体检测临界值为0.148;与细胞中和实验方法阳性符合率为100%,阴性符合率为92%,与柯萨奇 A16病毒抗体无交叉反应。②819名健康儿童血清标本中,男481名,女338名。<1岁组（60%,60/100名）和~2岁组（39.3%,72/183名）EV71-IgG抗体阳性率显著高于其他各年龄组［~3岁、~4岁、~5岁和~14岁组分别为12.9%（15/116名）、27.1%（38/140名）、14.2%（16/113名）和22.8%（38/167名）］。EV71-IgG抗体阳性率无显著性别差异。③4 780例EV71阳性HFMD患儿中,男3 070例,女1 718例。<1岁310例（6.5%）,~2岁1 157例（24.2%）,~3岁1 337例（28.0%）,~4岁1 094例（22.9%）,~5岁450例（9.4%）,~14岁432例（9.0%）。④各年龄组EV71-IgG抗体阳性率与EV71阳性年龄构成比呈相反趋势,<1岁组EV71-IgG抗体阳性率最高,EV71阳性年龄构成比最低;~3岁组EV71-IgG抗体阳性率最低,EV71阳性年龄构成比最高。结论 <1岁健康儿童EV71-IgG阳性率最高,EV71阳性年龄构成比与EV71-IgG阳性率呈相关现象。