Multiple viral respiratory pathogens in children with bronchiolitis

Aim: The aim of the study was to describe the frequency of viral pathogens and relative frequency of co-infections in nasal specimens obtained from young children with bronchiolitis receiving care at a children's hospital.
Methods: We conducted a study of nasal wash specimens using real-time PCR and fluorescent-antibody assay results from children less than two with an ICD-9-CM code for bronchiolitis. All specimens were collected for clinical care at Children's Hospital in Seattle, WA, USA, during the respiratory season from October 2003 to April 2004.
Results: Viruses were detected in 168 (93%) of the 180 children with bronchiolitis. A single virus was identified in 127 (71%) children and multiple viruses in 41 (23%). Respiratory syncytial virus (RSV) was the most common virus detected (77%), followed by adenovirus (15%), human metapneumovirus (11%), coronavirus (8%), parainfluenza (6%) and influenza (1%). Of the 139 samples with RSV detected, 34 (24%) were co-infected with another viral pathogen.
Conclusion: Molecular diagnostic techniques identified a high frequency of viruses and viral co-infections among children evaluated for bronchiolitis. Further study of the role of viral pathogens other than RSV and co-infections with RSV in children with bronchiolitis appears warranted.     

2000年冬-2006年春北京地区急性呼吸道感染患儿中呼吸道合胞病毒的监测

目的 对北京急性呼吸道感染患儿进行呼吸道合胞病毒（RSV）的监测并进行亚型分析,探讨其流行规律。方法 2000年11月-2006年3月,于首都儿科研究所附属儿童医院采集因急性呼吸道感染就诊的门诊及住院的患儿咽拭子或鼻咽分泌物标本10048份,接种于Hep-2细胞进行病毒分离,同时用免疫荧光法对鼻咽分泌物标本进行呼吸道病毒抗原的快速检测,对部分RSV阳性的标本用RT-PCR进行了亚型鉴定。结果 （1）在10048份标本中,有2286份为RSV阳性,阳性检出率为22．8％。其中病房标本7176份,RSV阳性2153份,阳性检出率为30．0％;门诊标本2872份,RSV阳性133份,阳性检出率为4．6％。（2）2000～2001年冬春、2002-2003年冬春、2004-2005年冬春RSV的阳性检出率分别为14．0％、18．2％和20．4％,而2001—2002年冬春、2003—2004年冬春和2005-2006年冬春RSV的阳性检出率分别为42．3％、41．0％和40．5％。（3）对938份RSV阳性标本的亚型监测结果：A亚型691份,占73．7％,B亚型247份,占26．3％,2000-2001、2004-2005年冬春季RSV感染以B亚型为主;而2001-2002、2002-2003、2003-2004年冬春季以A亚型为主;2005—2006年为A、B亚型同时流行。结论 RSV是冬春季婴幼儿下呼吸道感染的主要病毒病原,RSV呈现出隔年高峰的流行趋势,RSVA、B亚型是交替出现的,并且有时以相近的比例同时出现。     

Therapy for respiratory tract infections caused by respiratory syncytial virus

Respiratory syncytial virus (RSV) is the most common viral cause of lower respiratory tract infection (LRTI) in infancy and young children. No effective treatment for RSV lower respiratory tract infection (RSV-LRTI) exists. Ribavirin initially proved to be an effective anti-viral drug for RSV-LTRI. However, subsequently performed trials could not reproduce these positive results and, based on the current available evidence, there is no place for ribavirin in the routine treatment of RSV-LTRI. The use of nebulised bronchodilator therapy in RSV-LTRI has been subject of many trials, with conflicting results. Although the individual patient may have some short-term benefit from nebulised bronchodilators, there does not seem to be a sufficient scientific basis for the standard use of bronchodilator therapy in infants and children with RSV-LTRI. There is increasing evidence that RSV-LTRI is an immune-mediated disease and therefore corticosteroids may be an effective treatment. The results from efficacy trials have demonstrated that corticosteroids are not effective for patients with mild RSV infection. In contrast there are indications that it may be beneficial in patients with more severe RSV-LTRI. It has been demonstrated that in children with RSV infection the vitamin A concentration is inversely related to disease severity. The use of vitamin A in the treatment of patients with RSV-LTRI, however, proved not to be effective. Immunoprophylaxis with hyperimmune immunoglobulins and monoclonal antibody against the viral F-protein have been shown to be effective in the prevention of RSV-LRTI. From the results of the therapeutic efficacy trials, however, it can be discerned that immunoglobulins have no place in the treatment of RSV-LRTI. Conclusion Although respiratory syncytial virus infections each year have a considerable socioeconomic impact, attempts to find an effective therapy have so far been quite unsuccessful. Anti-viral therapy with ribavirin has not been proven to be effective. Symptomatic therapy with bronchodilators may give only short-term relief of symptoms in some individual patients, but has no effect on hospitalisation rates, or duration of hospitalisation. The beneficial effect of corticosteroids in patients with mild respiratory syncytial virus infection is very disappointing, however, there are indications that there might be an effect in patients with more severe infection. So far no beneficial therapeutic effect has been demonstrated with immune globulins. Received: 9 August 1999 / Accepted: 30 November 1999     

用免疫荧光方法检测鼻咽分泌物中多种呼吸道病毒抗原

目的 评价一种商品化的免疫荧光检测试剂用于呼吸道病毒感染诊断的敏感性及特异性。方法 间接免疫荧光方法,包括筛查及确定试验。筛查试剂中含有７种混合单克隆抗体,即甲型及乙型流感病毒,呼吸道合胞病毒,副流感病毒１,２,３型及腺病毒单克隆抗体。此外还有分别针对上述７种病毒的单克隆抗体用于确定试验。     

Association between multiple respiratory viral infections and pediatric intensive care unit admission among infants with bronchiolitis

BackgroundIt is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis.MethodsWe performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission.ResultsA total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3–4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6–6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P < 0.001). In the multivariable logistic regression analysis, bronchiolitis with multiple viral infections was associated with higher odds of PICU admission (adjusted odds ratio: 2.56, 95% confidence interval: 1.17–5.57, P = 0.02).ConclusionInfants with multiviral bronchiolitis have higher odds of PICU admission compared with those with a single or nondetectable viral infection.     

呼吸道合胞病毒毛细支气管炎患儿血和痰中白三烯测定及临床意义

目的 探讨呼吸道合胞病毒(respiratory syncytial virus,RSV)毛细支气管炎(毛支炎)患儿血、痰中白三烯C4(leukotriene C4,LTC4)水平的变化及临床意义.方法轻-中度毛支炎组22例,重度毛支炎组11例,另选择无喘息非RSV感染性肺炎患儿12例作为对照(肺炎组).采用双抗体夹心酶联免疫吸附试验测定血清和痰中LTC4水平,并进行对比分析.结果急性期轻-中度毛支炎组、重度毛支炎组、肺炎组血清LTC4水平分别为(76.96±28.19)pg/ml、(103.53±16.85)pg/ml、(18.14±7.49)pg/ml;痰中LTC4水平分别为(31.83±19.14)pg/ml、(67.11±15.11)pg/ml、(6.81±2.90)pg/ml;恢复期血清LTC4水平分别为(36.04±16.38)pg/ml、(52.27±17.03)pg/ml、(18.14±7.49)pg/ml,3组间差异有统计学意义(F=48.09,P＜0.001;F=15.50,P＜0.001;F=44.43,P＜0.001).治疗后轻-中度和重度毛支炎组血清LTC4水平明显降低,但仍高于肺炎组,差异有统计学意义(P＜0.05).结论RSV毛支炎患儿血和痰中LTC4水平明显增高,并与病情的轻重相关.     

呼吸道感染患儿呼吸道合胞病毒核酸扩增荧光定量检测及分析

目的：核酸扩增荧光定量PCR用于病原学诊断,是目前诊断呼吸道合胞病毒（RSV）感染的先进方法。通过检测呼吸道感染患儿RSV- RNA相关序列的存在,探讨其敏感性和RSV感染情况。方法：收集2007年1月至2008年10月该院儿科261例呼吸道感染住院患儿鼻咽部支气管分泌物标本,用核酸扩增荧光定量检测痰标本RSV核酸RNA。同时抽取静脉血用酶联免疫吸附法检测RSV-IgM作对照,比较两种方法的敏感性。结果：①痰标本RSV-RNA阳性率38.7%,血RSV-IgM阳性率21.1%,两种方法检测阳性率差异有显著性(P<0.01)。②年龄≤6个月组痰标本RSV-RNA阳性率43.6％,显著高于1～3岁组阳性率32.1％（P<0.01）。③毛细支气管炎痰标本RSV-RNA阳性率最高（58.5%）,与急性支气管炎和支气管肺炎痰标本比较,差异有显著性（P<0.01和<0.05）。结论：核酸扩增荧光定量PCR检测呼吸道RSV感染敏感性高,RSV是婴幼儿时期下呼吸道感染的主要病原,年龄越小感染率越高,毛细支气管炎感染率最高。［中国当代儿科杂志,2009,11（10）：825-828］     

新近发现的呼吸道病毒感染流行病学与临床研究进展

呼吸道感染是儿科常见病、多发病,病因复杂,其中病毒在儿童呼吸道感染中起重要作用.近年来新发现的呼吸道病毒包括人偏肺病毒、SARS冠状病毒、人冠状病毒NL63和HKU1、人博卡病毒以及人多瘤病毒,本文对其流行现状和临床研究进展作一介绍.     

急性呼吸道感染儿童两亚型呼吸道合胞病毒检测分析

目的 了解2006-2007年度重庆地区住院急性呼吸道感染(ARTIs)儿童两亚型呼吸道合胞病毒(RSV)的感染特点及流行规律.方法 收集2006年4月至2007年3月全年在重庆医科大学附属儿童医院呼吸科住院的部分ARTIs患儿的鼻咽深部吸取物390份,针对RSV G基因保守区序列设计分型引物,采用RT-PCR方法检测标本中RSV的基因组RNA.结果 390例标本中RSV阳性例数为133例(133/390,阳性率为34.10%).阳性标本中A亚型阳性129例,B亚型阳性4例.RSV阳性患儿中,84.9%为2岁以下小儿.2006年11月～2007年1月为RSV高发季节,RSV检测阳性率为55.6%～62.3%,2006年12月RSV检测阳性率最高.B亚型出现于本地区RSV感染低发季节(4、5、6月).RSV感染的临床表现主要为发热(56.4%)、咳嗽(98.5%)、喘息(63.9%)、气促(76.7%)、紫绀(84.9%).临床诊断依次为毛细支气管炎(33.1%),支气管肺炎(27.8%),间质性肺炎(18.1%),重症肺炎伴呼吸衰竭(10.5%),喘息性支气管炎(5.3%),支气管哮喘(4.5%).结论 本研究初步阐明了重庆地区两亚型RSV感染的流行病学特点,证实RSV是重庆地区冬春季婴幼儿ARI的重要病原,2006-2007年度以A亚型RSV流行为主.今后的研究将纳入门诊及社区惠儿并进行多年度连续监测以进一步阐明重庆地区两亚型RSV流行规律及病毒进化特点.     

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??Objective To investigate the clinical relevance of multiple viral infections in children with acute lower respiratory disease. Methods A total of 1722 children with clinical diagnosis of lower respiratory tract infection ??ALRTI?? during the period of October 2007 to September 2011 were involved in our study. One nasopharyngeal aspirate specimen was collected from each patient. ??RT?? PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus ??RSV?? ?? rhinovirus ??RV?? ?? influenza virus type A and B?? parainfluenza virus ??PIV?? type 1-4?? adenovirus ??enterovirus?? human coronavirus?? human metapneumonia virus and human bocavirus. Results Totally 206 children had single RSV infection?? 124 children had dual infections ??RSV co-infected with an additional virus?? and 40 children had multiple infections along with a RSV infection. Out of the 124 patients?? 68??54.8%?? were co-infected with RV?? 24 with PIV. There was a statistically significant difference between the dual viral infections group and the RSV-infected group in hospital stay??P??0.001??. Compared to patients in the single RSV infected group?? patients in the multiple viral infection group had significantly more frequency in fever ??P??0.017???? duration of fever longer??P??0.015???? hospital stay also longer??P??0.001????and they received more intravenous steroid therapy during hospitalization??P??0.005??. There was no significant difference in oxygen therapy?? respiratory support and use of bronchodilators. Conclusion Multiple viral infections are linked to more frequency in fever?? longer fever days?? longer hospital stay?? and more frequent use of intravenous steroid therapy during hospitalization. Mixed respiratory virus infection may affect the patient's disease severity and prognosis.     

Human metapneumovirus infections cause similar symptoms and clinical severity as respiratory syncytial virus infections

Human metapneumovirus (hMPV) is a recently discovered pathogen in respiratory tract infection. The published literature suggests milder illness severity in hMPV compared with respiratory syncytial virus (RSV) infection. In two consecutive seasons, 637 nasopharyngeal aspirates from pediatric patients were tested by hMPV polymerase chain reaction, and risk factors and clinical and laboratory items were analyzed. The hMPV patients were compared with hMPV-negative but RSV-positive patients by matched pair analysis. HMPV was detected in 17.9% of all samples. In total, 88 hMPV-infected patients with complete datasets were considered. More than half of all hMPV patients were older than 12 months, 45.5% had at least one risk factor for a severe course of viral respiratory tract infection, and 27.3% were born prematurely, 15.9% with a birth weight <1,500 g. At least one other virus was also detected in 39 patients (44.3%; RSV in 29.5%). Coinfection did not result in greater severity of illness. On matched pair analysis (hMPV-positive/RSV-negative vs. hMPV-negative/RSV-positive), the epidemiological and clinical features of hMPV infection were similar to those of RSV infection, as in the hMPV group higher proportions of patients with hypoxemia on admission (33% vs. 21%) and of intensive care treatment (20.8% vs. 10.4%) were observed. More hMPV patients showed lobar infiltrates in radiological chest examination. In 60% of all hMPV infections, the attending physicians prescribed antimicrobial chemotherapy. We conclude that in hospitalized children, hMPV infection is as serious as RSV infection and therefore deserves the same attention. Virologic diagnosis from respiratory secretions is mandatory because clinical, laboratory, and radiological signs cannot sufficiently discriminate between viral and bacterial respiratory tract infection in infants and children.The first two authors contributed equally to this work.     

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??Respiratory infections??especially respiratory viral infections??are common diseases in children. Although most respiratory viral infection diseases are self-limiting??some children may be hospitalized or even life-threatened due to severe viral lower respiratory tract infection. With the progress of virology research??new and effective antiviral drugs have been developed. Thus??the study focuses on the therapeutic progress of respiratory viral infections so as to improve the treatment for common respiratory viral infections in children.     

Pneumomediastinum,pneumorrhachis and subcutaneous emphysema associated with viral infections: Report of three cases

Spontaneous pneumomediastinum is usually secondary to alveolar rupture in the pulmonary interstitium, associated with subcutaneous emphysema and occasionally with pneumothorax, but is rarely associated with pneumorrhachis. The leaked air into the pulmonary perivascular interstitium follows the path of least resistance from the mediastinum to the fascial planes of the neck. Air freely communicates via the neural foramina and collects in the epidural space. Pneumorrhachis is defined as the presence of air in the spinal canal, either in the intradural and/or extradural spaces. It is a very rare clinical entity and mostly asymptomatic, hence most probably underdiagnosed. Many pathological and physiological events can lead to alveolar rupture, and these clinical findings can be related to various, mainly traumatic and iatrogenic etiologies. Herein we report three cases of pneumomediastinum, subcutaneous emphysema, interstitial emphysema and pneumorrhachis in two cases, which were related to rhinovirus, human bocavirus and respiratory syncytial virus infection.     

小儿呼吸道合胞病毒感染流行特点分析

目的探讨小儿呼吸道合胞感染病毒感染的流行特点及影响RSV流行的气候因素。方法对2001年1月至2006年12月因下呼吸道感染在浙江大学医学院附属儿童医院住院的39597例患儿取鼻咽分泌物标本进行呼吸道合胞病毒(RSV)抗原检测。结果39597例患儿中RSV检测阳性患儿共8657例(21.86%),<1岁者6804例(30.99%),1～3岁者1576例(14.84%),～13岁者277例(3.95%),各年龄组间检出率有统计学意义(P<0.01)。男性5783例(22.76%)高于女性2873例(20.24%),有统计学意义(P<0.01)。RSV检出率与气温之间存在直线负相关,气温每升高1℃,下呼吸道感染患儿中RSV的检出率下降1.8%。冬季是RSV流行高峰,其次是春季和秋季,夏季RSV感染率最低,全年都有RSV的散发流行。结论RSV是冬春季节引起小儿下呼吸道感染的主要病毒,年龄越小RSV感染率越高,男性较女性易感RSV。气温越低,RSV的检出率越高,低气温是杭州地区RSV流行的重要因素之一。     

潘生丁对呼吸道合胞病毒肺炎治疗作用的实验研究

目的探讨潘生丁（ＤＰＭ）对呼吸道合胞病毒（ＲＳＶ）肺炎的治疗作用。方法采用光镜、电镜观察肺组织形态等方法，对ＲＳＶ肺炎组与ＲＳＶ肺炎＋ＤＰＭ处理组的小鼠进行了对比观察。结果ＤＰＭ处理组小鼠肺组织病毒滴度明显低于肺炎组（Ｐ＜０．０１）；ＲＳＶ肺炎组小鼠肺间质较多淋巴细胞浸润，肺泡隔重度增宽和实变，毛细血管严重瘀血、血小板聚集和血栓形成；巨噬细胞溶酶体少，残余体堆积；ＤＰＭ处理组小鼠肺间质浸润淋巴细胞少，肺泡隔轻、中度增宽，无实变；毛细血管无瘀血、血小板聚集和血栓形成；巨噬细胞内大量溶酶体，吞噬活跃。结论ＤＰＭ能抗ＲＳＶ肺炎血管内血小板聚集和血栓形成，减少Ｔ淋巴细胞增生和浸润，提高巨噬细胞吞噬病毒能力     

白细胞介素8单核苷酸多态性与呼吸道合胞病毒易感性关联的研究

目的探讨白细胞介素8（IL-8）-251T／A和781C／T单核苷酸多态性（SNP）与呼吸道合胞病毒（RsV）易感性的关系。方法采用等位基因特异性聚合酶链反应（AS—PCR）技术,对101例RSV肺炎、108例非RSV肺炎住院患儿及35个核心家系的两个SNP位点的基因型进行检测,通过基因测序进行验证。用病例-对照和传递不平衡检验（TDT）分析SNP位点等位基因的分布,并对两个SNP位点的连锁和单体型进行分析。结果（1）病例组IL-8—251T的频率显著增加（OR=2．08,P=0．0002,病例-对照分析;LRT=14．31,P=0．0008,VDT）。（2）IL-8—251T与781C是连锁的（D’=0．607±0．03,r^2=0．2861,P=0．0000）。（3）病例组TC单体型的频率显著增加（P=0．01）。结论IL-8—251T与781C形成的TC单体型与RSV易感性存在关联,即部分RSV易感基因可能存在于含有TC单体型的基因片段中或者与该段基因紧密连锁。