Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database

Premature birth, chronic lung disease of prematurity (CLD), congenital heart disease and immunodeficiency predispose to a higher morbidity and mortality in respiratory syncytial virus (RSV) infection. This study describes the preterms hospitalised with RSV infection from the prospective German DSM RSV Paed database. The DMS RSV Paed database was designed for the prospective multicentre documentation and analysis of clinically relevant aspects of the management of inpatients with RSV infection. This study covers six consecutive RSV seasons (1999–2005); the surveillance took place in 14 paediatric hospitals in Germany. Of the 1,568 prospectively documented RSV infections, 26% (n = 406) were observed in preterms [vs. 1,162 children born at term (74%)] and 3% (n = 50) had CLD, of which 49 had received treatment in the last 6 months (‘CLDplus’). A significantly higher proportion in the preterm group had congenital heart disease, nosocomial infection, and neuromuscular impairment. There were significantly more children older than 24 months in the preterm group. The attributable mortality was 0.2% (n = 2) in children born at term vs. 1.2% (n = 5) in the preterm group (p = 0.015) [preterm plus CLD 8.0% (n = 4 of 50); McIntosh grade 1, 8.6% (n = 3 of 35) and McIntosh Grade 4, 15% (n = 3 of 20)]. Eight patients were categorized as ‘palivizumab failures’. In the multivariate analysis, premature birth, CLD_plus, and nosocomial infection were significantly and independently associated with the combined outcome ‘complicated course of disease’. In conclusion, this is the first prospective multicentre study from Germany that confirms the increased risk for severe RSV disease in preterms, in particular in those with CLD treated in the last 6 months before the onset of the infection. From the perspective of our results, the statements of the German Society of Paediatric Infectious Diseases considering the use of passive immunisation (2003) seem reasonable.     

Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden

Aim: To investigate the cost‐effectiveness of palivizumab vs. no prophylaxis for respiratory syncytial virus (RSV) infection in preterm infants in Sweden. Methods: A probabilistic Markov model was populated using a nationwide register linkage and data from the literature. Cost‐effectiveness was investigated from a societal perspective over a lifetime for infants born at <29 weeks of gestation. Palivizumab was modelled using assumptions for its direct effect on RSV hospitalization risk and an indirect effect (via decreased RSV hospitalization) on subsequent asthma and mortality during the epidemic. Costs and effects were discounted by 3%. Results: In the base case, prophylaxis resulted in an additional 0.102 quality‐adjusted life‐year (QALY) at a cost of 20 000 SEK relative to no prophylaxis (incremental cost‐effectiveness ratio [ICER] 195 000 SEK/QALY). The probability of prophylaxis being cost–effective was 99% at a willingness‐to‐pay of 500 000 SEK/QALY. Assumptions about a causal association between RSV infection and subsequent asthma had a moderate impact, while exclusion of the indirect prophylaxis effect on mortality increased the ICER to 492 000 SEK/QALY. When excluding both of these, prophylaxis was not cost–effective. Conclusion: Based on a willingness‐to‐pay of 500 000 SEK/QALY, palivizumab was found to be cost–effective compared with no prophylaxis for infants born at <29 weeks if severe RSV infection was assumed to increase subsequent asthma or mortality risk.     

Prophylaxis of respiratory syncytial virus in Canada in 2003

Passive immunization of high-risk children with the humanized monoclonal antibody palivizumab is the mainstay of respiratory syncytial virus (RSV) prophylaxis in Canada in 2003. This product appears to be safe, and it prevents the majority of RSV hospitalizations in infants born before 36 weeks gestational age, and about half in children under 24 months of age with hemodynamically significant congenital heart disease. However, the high cost of palivizumab and the fact that at least 12 infants need to be treated throughout RSV season to prevent one hospitalization make it difficult to determine the ideal indications for the product. Because these high-risk infants account for a minority of RSV hospitalizations, it is desirable to search for a prophylactic strategy that is practical to apply in all infants.     

International variation in the management of infants hospitalized with respiratory syncytial virus

Respiratory syncytial virus (RSV) is a frequent cause of hospitalization among infants. To compare patient management in Europe, the United States, and Australia, we analyzed the charts of 1,563 pediatric patients hospitalized with laboratory-confirmed RSV lower respiratory infections during recent RSV seasons. Half of patients had been seen initially as outpatients. Median duration of hospitalization was 4 days in Australia, Finland, the United Kingdom, and the United States, and 8 or 9 days in Belgium, France, Germany, Italy, and the Netherlands. In a linear regression model that included clinical findings, underlying conditions, prematurity, and age, the leading variable associated with length of stay was “hospitalization in continental Europe”. This geographic factor conferred a 1.8-fold longer stay (95% CI: 1.7–1.9) than hospitalization elsewhere. Utilization of nine supportive therapies for RSV varied widely among hospitals, even within the same country. The individual hospital was strongly associated with the use of every therapy studied, independent of patient characteristics and clinical status. Conclusion Management of RSV patients varies markedly by country and hospital. Multicenter RSV trials that measure length of stay should standardize criteria for “readiness for discharge”. It may be appropriate to limit international trials to countries with similar median stays for RSV. Variability within multicenter trials could be further controlled by standardizing the use of other therapies and the diagnosis of complications. Received: 29 April 1997 / Accepted in revised form: 11 August 1997     

新生儿和婴儿呼吸道合胞病毒致急性下呼吸道感染临床特征和疾病负担

目的了解上海地区新生儿和婴儿呼吸道合胞病毒（RSV）感染的严重程度及疾病负担,为RSV感染的监测及临床防治提供科学依据。方法回顾性收集2012年3月至2013年2月复旦大学附属儿科医院内科和新生儿科住院并确诊为急性下呼吸道感染（ALRI）≤1岁患儿的病历,截取人口学资料、临床特征、病死率、并发症、住院时间和费用等指标,并采用严重度指数(SI)进行RSV感染严重程度综合评价。分为新生儿组和婴儿组,并进一步分为单一感染和混合感染亚组进行分析。 结果1 726例ALRI≤1岁患儿中RSV阳性913例（52.9%）进入分析。新生儿组295例,婴儿组618例。①SI评分新生儿组高于婴儿组,(2.5±0.2) vs (1.9±0.1)分,P<0.05;较重度和重度比例新生儿组显著高于婴儿组,但单一感染和混合感染亚组间差异无统计学意义。②RSV感染的≤1岁患儿病死率为5.0％,新生儿组病死率与婴儿组差异无统计学意义,婴儿组合并基础疾病患儿病死率高。③机械通气比例两组间差异无统计学意义,婴儿组混合感染亚组高于单一感染亚组。④并发症情况：新生儿组呼吸暂停和脓毒症发生率较高,新生儿组混合感染亚组脓毒症发生率显著高于单一感染亚组。⑤住院天数新生儿组与婴儿组差异无统计学意义,合并基础疾病者显著高于未合并疾病疾病患儿;住院费用婴儿组显著高于新生儿组,新生儿混合感染亚组显著高于单一感染亚组,合并基础疾病患儿显著高于未合并基础疾病患儿。 结论RSV感染新生儿的重症比例和并发症的发生率较高,婴儿组住院费用较高。混合感染和合并基础疾病是影响RSV感染严重程度和疾病负担的重要因素。     

Bronchiolitis due to respiratory syncytial virus in hospitalized children: a study of seasonal rhythm

AIM: The objective of this study was to describe the rhythm of respiratory syncytial virus (RSV) bronchiolitis seasonal outbreaks in hospitalized children. METHODS: Data was collected from 1324 patients, who were admitted to our hospital with bronchiolitis, over an 11-year period, from 1994 to 2004. The epidemic onset was established according to the epidemic index. Virological diagnosis was made with immunofluorescent assay from nasopharyngeal washings. Rhythm study was carried-out by spectral analysis with the fast-Fourier transformed and cosinor method. RESULTS: Epidemics begin in September (45%) and October (55%); the highest peak was observed in January, the minimum in August and the end in February (73%), March (18%) and April (9%). When the epidemic outbreak begins sooner, the end is sooner as well. Epidemic onset varies but not its length and the onset was less variable than its conclusion. Spectral analysis showed a 12-months cyclic period along the study years and cosinor analysis demonstrated significant circannual rhythm. When data was segregated by long and short hospital stay, no significant differences were found between the rhythms. Comorbid association among bronchiolitis, otitis and gastroenteritis was very common. CONCLUSION: Bronchiolitis epidemics onset and conclusion varies along time years in hospitalized infants and showed circannual rhythmicity with a 12-months period.     

Use of permissive hypercapnia in the ventilation of infants with respiratory syncytial virus infection

We wished to retrospectively evaluate the effects of permissive hypercapnia (PHY) on barotrauma, mortality and length of stay when applied to ventilated infants with respiratory syncytial virus (RSV) bronchiolitis. Nineteen control infants with RSV induced respiratory failure were treated with conventional ventilation (April 1991–January 1994), after which time PHY was adopted as unit policy. A further 28 infants were then treated with PHY (January 1994–April 1996). Demographic and physiological data were collected from admission, and outcome variables including length of stay, barotrauma and mortality were recorded. The PHY group showed a significantly higher mean pCO₂ (7.6 vs 5.2 kPa), a lower mean pH (7.34 vs 7.40), and a reduction in maximal peak inspiratory pressures (25 vs 30 cmH₂O). Mortality, barotrauma, use of neuromuscular blockade and nosocomial infection did not differ between groups. There was a trend towards increased length of ventilation in the PHY group (median 7 vs 5 days). Conclusion Based on this retrospective data we can show no benefit for the use of permissive hypercapnia as a ventilatory strategy in this patient group. A prospective randomised controlled trial is warranted to accurately assess the outcome variables and cost implications of this strategy. Received: 22 June 1998 / Accepted in revised form: 25 August 1998     

Risk factors for mechanical ventilation in respiratory syncytial virus infection

In a prospective study, risk factors for mechanical ventilation were identified in 102 patients with respiratory syncytial virus (RSV) infection admitted to the Sophia Children's Hospital, Rotterdam. Age, weight on admission and prematurity were associated with the need for mechanical ventilation. Using multivariate analysis, only low weight was an independent risk factor for mechanical ventilation. For infants weighing less than 5 kg the relative risk for mechanical ventilation was 4.4 (95% confidential interval 1.3–13.9).     

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     

下呼吸道感染患儿外周血单个核细胞呼吸道合胞病毒感染的研究

为探讨呼吸道合胞病毒（ＲＳＶ）对外周血单个核细胞（ＰＢＭＣ）的感染情况及感染后细胞免疫的变化，采用免疫组化法对１８例ＲＳＶ性急性下呼吸道感染患儿ＰＢＭＣ内ＲＳＶ及其Ａ、Ｂ亚型抗原进行了检测；采用ＡＰＡＡＰ法、ＭＴＴ比色法和ＥＬＩＳＡ法对Ｔ细胞亚群及Ｔ细胞表面白细胞介素２受体表达、ＰＢＭＣ培养上清液白细胞介素２（ＩＬ－２）活性和可溶性ＩＬ－２受体水平进行了测定。结果显示：１８例ＲＳＶ感染患儿中７例ＰＢＭＣ内可检测到ＲＳＶ抗原；１１例ＲＳＶＡ亚型感染者５例ＰＢＭＣ内均为ＲＳＶＡ亚型阳性，７例ＲＳＶＢ型感染者２例Ｂ亚型阳性；７例恢复期和１０例对照组患儿均为阴性；发病３天以内ＰＢＭＣ中ＲＳＶ抗原阳性者多于３天以后（Ｐ＜０．０５）。ＲＳＶ感染组ＰＢＭＣ内ＲＳＶ抗原阳性者，ＣＤ４细胞比率和ＩＬ－２水平均低于阴性者（ｔ＝２．３８，２．４０，Ｐ值均＜０．０５）。提示：ＲＳＶ性急性下呼吸道感染患儿ＰＢＭＣ可被ＲＳＶ感染，可能由此加重免疫活性细胞损害，导致细胞免疫功能紊乱。     

Burden of respiratory syncytial virus infection in young children

Respiratory syncytial virus (RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants (below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-risk infants, lowers the burden of RSV infection in certain carefully selected patient groups.     

Current respiratory syncytial virus prevention strategies in high-risk infants

Respiratory syncytial virus (RSV) was initially isolated in 1956. Since then it has become recognized as a major pathogen worldwide. It is a ubiquitous pathogen that produces seasonal epidemics. Primary infection occurs in children before 2 years of age. In older children and adults, RSV usually manifests itself as an upper respiratory tract infection. In immunecompromised patients, those with underlying cardiopulmonary disorders, premature infants, and other vulnerable individuals, RSV infection can produce severe bronchiolitis or pneumonia. In recent years we have observed exciting new information about the prevention of serious RSV infection in high-risk infants including infection control practices, active immunity and passive immunity. Two immunoprophylaxis products (RSV i.v. immune globulin and palivzumab) have been developed for clinical use in the prevention of serious RSV infection. Many other agents including vaccines, super monoclonal antibodies, and antivirals are under development. Although clinicians now have the ability to provide their most vulnerable patients with meaningful prevention strategies, much more needs to be done before we can regard RSV as a preventable disease.     

Risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection in children

BACKGROUND: Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract infection that can be a life-threatening disease in infants and children. This study was conducted to look for independent risk factors for severe respiratory syncytial virus-associated lower respiratory tract infection (RSV-LRI) that required oxygen supplementation or mechanical ventilation. METHODS: Medical records of patients younger than 4 years hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from July 1, 1995 to June 30, 1999 were reviewed. The patients were compared using univariate and multivariate logistic regression analysis. RESULTS: A total of 157 patients were hospitalized with RSV-LRI at Shizuoka Red Cross Hospital from the study time period. Of these, 20 patients (12.7%) were diagnosed with severe RSV-LRI. Subjects younger than 3 months of age had an odds ratio (OR) of 59.9 (95% confidence interval (CI) 14.7_244.0) for the dependent variable of severe RSV-LRI (P<0.0001). Subjects with a history of congenital heart disease also had an OR of 99.2 (95% C1 8.5-1160.1) (P<0.0005). CONCLUSIONS: Infants younger than 3 months without any underlying diseases may be at high risk for severe RSV-LRI. Respiratory syncytial virus prophylaxis is needed not only for high-risk patients, but for healthy early infants.     

WU多瘤病毒与呼吸道合胞病毒感染患儿临床特征比较

目的探讨和比较WU多瘤病毒(WUPyV)以及呼吸道合胞病毒(RSV)所致呼吸道感染患儿的临床特征。方法应用多重PCR技术,检测呼吸道感染住院患儿WUPyV、RSV等病毒感染情况,并收集WUPyV和RSV感染患儿的临床资料。结果 2008年1月至2010年9月,在1 701例呼吸道感染住院患儿的咽拭子标本中检测出WUPyV阳性46例(2.7%),RSV阳性365例(21.5%);单纯WUPyV感染为22例(47.8%),单纯RSV感染为88例(24.1%)。RSV感染患儿的合并感染率高于WUPyV感染患儿,两者差异有统计学意义(χ2=11.723,P=0.001)。WUPyV阳性检测率在春季呈现高峰,RSV则在冬季。WUPyV感染患儿的中位年龄为26.2个月,RSV感染患儿为14.9个月,两者差异有统计学意义(U=669.5,P<0.05)。WUPyV感染患儿的临床表现和体征与RSV感染相似,咳嗽(χ2=13.34,P<0.001)和喘息(χ2=10.53,P<0.001)在RSV感染的患儿中更为多见。WUPyV感染后主要被诊断为支气管肺炎,而RSV感染后主要为毛细支气管炎。单纯RSV感染患儿更多需要激素治疗(χ2=9.321 P=0.002)。结论部分患儿呼吸道感染与WUPyV感染有关,WUPyV感染的临床特征与RSV感染类似。     

早产儿院内感染危险因素及病原学分析

目的：分析早产儿院内感染发生的高危因素及病原学特点。方法：对197例早产儿院内感染情况进行回顾性分析。结果：住院早产儿院内感染发生率为22.2％(197/887)。胎龄小、低出生体重、机械通气治疗、延迟喂养是早产儿发生院内感染的重要高危因素。肺炎克雷伯菌在院内感染中占据首位(22.3%),其次为葡萄球菌(18.4%)。结论：对胎龄小、低出生体重的早产儿应强调以洗手为中心的消毒隔离制度,尽量减少侵入性操作,尽早开始胃肠道喂养,以减少早产儿院内感染的发生。肺炎克雷伯菌是早产儿院内感染的主要病原菌。［中国当代儿科杂志,2009,11（12）：980-982］     

呼吸道合胞病毒下呼吸道感染外周血Th细胞亚群的研究

为探讨RSV下呼吸道感染辅助性T淋巴细胞CD4~+及其亚群CD4~+CD45RA~+、CD4~+CD45RO~+的表达及其意义,用单克隆抗体双色免疫荧光PE/FITC双标记,流式细胞仪检测30例RSV下呼吸道感染患儿急性期外用血单个核细胞(PBMCs)辅助性T淋巴细胞 CD4~+及其亚群CD4~+CD45RA~+、CD4~+CD45RO~+的表达;同时检测15例年龄、性别无差异的健康儿为对照。结果显示,RSV下呼吸道感染组患儿外周血辅助性T淋巴细胞CD4~+明显低于对照组(P<0.05);CD4~+CD45RA~+细胞明显下降(P<0.05);CD4~+CD45RO~+细胞虽稍有下降,但与对照组相比无统计学差异(P>0.05);CD4~+CD45RA~+/CD4~+CD45RO~+比值与对照组相比明显降低(P<0.05)。表明婴幼儿RSV下呼吸道感染急性期的免疫功能紊乱主要表现为辅助性T淋巴细胞CD4~+及其亚群CD4~+CD45RA~+/CD4~+CD45RO~+的失衡。     

The clinical features of respiratory syncytial virus: Lower respiratory tract infection after upper respiratory tract infection due to influenza virus

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are the primary pathogens of respiratory tract infection. However, epidemics of influenza virus infection have been observed to interrupt RSV epidemics (termed an epidemiological interference effect). METHODS: At a clinic in Tsuna county, Hyogo prefecture, Japan, a total of 1262 outpatients under 6 years of age with lower respiratory tract infection due to RSV (RSV-LRTI) and upper respiratory tract infection due to influenza virus (FLU-URTI) in three successive winter seasons (1999-2000, 2000-2001 and 2001-2002) were analyzed. RESULTS: The RSV-LRTI epidemic and FLU-URTI epidemic overlapped in each season, but the RSV-LRTI epidemic peak preceded that of the FLU-URTI epidemic. Epidemiological interference between RSV and influenza virus was observed in the second and third season; the number of patients with RSV-LRTI began to decrease after the start of the FLU-URTI epidemic and recovered to some extent after the FLU-URTI epidemic passed its peak. There were no differences in onset age, male-to-female ratio and severity of RSV-LRTI in outpatients before and after the start of the FLU-URTI epidemic in all the three seasons. CONCLUSION: An epidemiological interference between RSV and influenza virus was observed in Tsuna county in two of the three winter seasons. However, there was no difference between the clinical features of the patients with RSV-LRTI before and after the start of the influenza virus infection epidemic. The data suggest that the clinical severity of RSV infection is not changed by the epidemiological interference effect of influenza virus infection epidemics.